U.S. patent application number 16/509570 was filed with the patent office on 2020-04-02 for devices and methods for treating acute kidney injury.
The applicant listed for this patent is RENALPRO MEDICAL, INC.. Invention is credited to Charles Char-Lin Koo, Tsung-Chun Lee, Wen-Pin Shih.
Application Number | 20200100793 16/509570 |
Document ID | / |
Family ID | 60203588 |
Filed Date | 2020-04-02 |
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United States Patent
Application |
20200100793 |
Kind Code |
A1 |
Koo; Charles Char-Lin ; et
al. |
April 2, 2020 |
DEVICES AND METHODS FOR TREATING ACUTE KIDNEY INJURY
Abstract
A catheter devices/systems and methods therefrom are described
herein for treating acute kidney injury, especially the
contrast-induced acute kidney injury wherein the devices may
prevent the contrast dyes from entering into kidney and/or
facilitate blood flow of kidney by said catheter system.
Inventors: |
Koo; Charles Char-Lin; (Palo
Alto, CA) ; Lee; Tsung-Chun; (New Taipei City,
TW) ; Shih; Wen-Pin; (Taipei, TW) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RENALPRO MEDICAL, INC. |
Santa Clara |
CA |
US |
|
|
Family ID: |
60203588 |
Appl. No.: |
16/509570 |
Filed: |
July 12, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15969050 |
May 2, 2018 |
10441291 |
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16509570 |
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PCT/US17/31153 |
May 4, 2017 |
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15969050 |
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62331975 |
May 4, 2016 |
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62372450 |
Aug 9, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 6/12 20130101; A61M
25/09 20130101; A61B 2090/063 20160201; A61B 17/12045 20130101;
A61M 2025/1095 20130101; A61B 90/06 20160201; A61M 2025/0002
20130101; A61M 2210/1082 20130101; A61M 1/106 20130101; A61B
2090/064 20160201; A61M 25/1011 20130101; A61B 17/12131 20130101;
A61M 25/0108 20130101; A61M 2210/12 20130101; A61M 2205/0266
20130101; A61B 17/12172 20130101; A61M 2025/1079 20130101; A61M
2205/3331 20130101; A61M 5/007 20130101; A61B 2017/00455 20130101;
A61B 17/12109 20130101; A61B 2090/3966 20160201; A61M 1/125
20140204; A61M 2025/0073 20130101; A61M 25/1002 20130101; A61B
17/1204 20130101; A61M 2205/0244 20130101; A61M 2206/16 20130101;
A61B 17/12136 20130101; A61M 1/1086 20130101; A61B 17/12031
20130101; A61B 6/484 20130101; A61M 2025/1052 20130101; A61B
17/12036 20130101; A61M 2205/3327 20130101 |
International
Class: |
A61B 17/12 20060101
A61B017/12; A61B 6/12 20060101 A61B006/12; A61B 6/00 20060101
A61B006/00; A61M 5/00 20060101 A61M005/00; A61M 25/01 20060101
A61M025/01; A61M 25/10 20060101 A61M025/10; A61B 90/00 20060101
A61B090/00 |
Claims
1. A method of preventing acute kidney injury from contrast agent
introduced into vasculature of a subject, the method comprising:
positioning a proximal portion of a catheter device comprising a
catheter shaft and an occlusive element in an abdominal aorta of
the subject adjacent renal artery ostia of the subject, wherein one
or more longitudinal position indication features are disposed on
the occlusive element; deploying the occlusive element of the
catheter device to occlude the renal artery ostia; confirming
occlusion of the renal artery ostia when the occlusive element is
deployed by observing the appearance of the one or more
longitudinal position indication features; introducing a bolus of
the contrast agent into the abdominal aorta of the subject while
the occlusive element is deployed to occlude the renal artery
ostia, thereby preventing the contrast agent from entering into
renal arteries of the subject; and collapsing the occlusive element
after the bolus of the contrast agent has been introduced, thereby
allowing blood flow to the renal arteries to resume.
2. The method of claim 1, wherein positioning the proximal portion
of the catheter device comprises observing a position of one or
more position indication features and positioning the proximal
portion of the catheter device in response to the observed
position.
3. The method of claim 2, wherein the one or more position
indication features comprise a radio-opaque marker, and wherein
observing the one or more position indication feature is done using
x-ray imaging.
4. The method of claim 1, wherein confirming occlusion of the renal
artery ostia comprising observing the appearance of a bowed section
in the one or more longitudinal position indication features.
5. The method of claim 1, wherein the one or more longitudinal
position indication features comprises one or more longitudinal
radio-opaque markers and wherein the bowed section is observed
using x-ray imaging.
6. The method of claim 1, wherein positioning the proximal portion
of the catheter device comprises observing a orientation of an
orientation element disposed on a distal portion of the catheter
device and positioning the proximal portion of the catheter device
in response to the observed orientation, wherein the orientation
element is aligned with the occlusive element and configured to
indicate the orientation of the occlusive element when positioned
adjacent renal artery ostia of the subject.
7. The method of claim 1, wherein the occlusive element comprises a
first expandable member disposed on a first lateral side of the
proximal portion and a second expandable member disposed on a
second lateral side of the proximal portion, wherein deploying the
occlusive element comprises expanding the first and second
expandable members, and wherein collapsing the occlusive element
comprises collapsing the first and second expandable members.
8. The method of claim 1, wherein expanding the first and second
expandable members comprises simultaneously expanding the first and
second expandable members.
9. The method of claim 1, wherein collapsing the occlusive element
comprises collapsing the occlusive element after a pre-determined
amount of time.
10. The method of claim 1, wherein deploying the occlusive element
and introducing the bolus of the contrast agent are synchronized.
Description
CROSS-REFERENCE
[0001] This application is a divisional application of Ser. No.
15/969,050 (Attorney Docket No. 45398-704.301), filed May 2, 2018,
which is a continuation of PCT/US2017/031153 (Attorney Docket No.
45398-704.601, formerly 45398-703.602), filed on May 4, 2017, which
claims the benefit of U.S. Provisional Application No. 62/331,975
(Attorney Docket No. 45398-704.101, formerly 45398-703.105), filed
May 4, 2016, and U.S. Provisional Application No. 62/372,450
(Attorney Docket No. 45398-704.102, formerly 45398-703.106), filed
Aug. 9, 2016, the entire contents of each of which is incorporated
herein by reference.
BACKGROUND
[0002] Acute kidney injury (AKI), also called acute renal failure
(ARF), is a rapid loss of kidney function. The causes of AKI are
numerous and may include low blood volume, decreased blood flow to
the kidneys, exposure of the kidney to toxic substances, or urinary
tract obstruction. AKI is diagnosed on the basis of clinical
history and laboratory data. Kidney function may be measured by
serum creatinine or urine output, among other tests, and a rapid
reduction in either or both of these factors may be diagnosed as
AKI.
[0003] One possible cause of AKI is the use of intravascular
iodinated contrast media or contrast agents. Contrast-induced AKI
(CI-AKI) is a common problem in patients receiving intravascular
iodine-containing contrast media for angiography. CI-AKI is
associated with excessive hospitalization cost, morbidity, and
mortality. Clinical procedures involving intravascular
iodine-containing contrast media injection may include, for
example, percutaneous coronary intervention (PCI), peripheral
vascular angiography and intervention, transarterial heart valve
interventions, and neurological angiography and intervention. In
clinical practice, CI-AKI is diagnosed when serum creatinine levels
increase by more than either 25% or 0.5 mg/dL above baseline within
48 to 72 hours of exposure to contrast media in the absence of
other culprit etiology for AKI.
[0004] Management of AKI hinges on identification and treatment of
the underlying cause. Additionally, management of AKI routinely
includes avoidance of substances toxic to the kidneys, called
nephrotoxins. Nephrotoxins include, for example, non-steroidal
anti-inflammatory drugs (NSAIDs), such as ibuprofen, iodinated
contrast agents, such as those used for CT scans, many antibiotics,
such as gentamicin, and a range of other substances.
[0005] Renal function monitoring by serum creatinine and urine
output is routinely performed. For example, insertion of a urinary
catheter helps monitor urine output and relieves possible bladder
outlet obstruction, such as with an enlarged prostate. In prerenal
AKI without fluid overload, administration of intravenous fluids is
typically the first step to improve renal function. Volume status
may be monitored with the use of a central venous catheter to avoid
over- or under-replacement of fluid. Should low blood pressure
prove a persistent problem in the fluid-replete patient, inotropes
such as norepinephrine and dobutamine may be given to improve
cardiac output and enhance renal perfusion. Also, while a useful
pressor, there is no evidence to suggest that dopamine is of any
specific benefit, and may in fact be harmful.
[0006] The myriad causes of intrinsic AKI can require specific
therapies. For example, intrinsic AKI due to Wegener's
granulomatosis may respond to steroid medication while
toxin-induced prerenal AKI often responds to discontinuation of the
offending agent, which may for example be aminoglycoside,
penicillin, NSAIDs, or paracetamol. Obstruction of the urinary
tract may also cause AKI and treatment may require relief of the
obstruction, for example with a nephrostomy or urinary
catheter.
[0007] Renal replacement therapy, such as with hemodialysis, may be
instituted in some cases of AKI. A systematic review of the
literature in 2008 shows no difference in outcomes between the use
of intermittent hemodialysis and continuous venovenous
hemofiltration (CVVH). Among critically ill patients, intensive
renal replacement therapy with CVVH does not appear to improve
outcomes compared to less intensive intermittent hemodialysis.
[0008] Current prevention strategies for AKI, particularly for
CI-AKI, are mainly supportive. They include for example (1)
evaluating and stratifying patients with Mehran risk score before
performing PCI, (2) avoiding high-osmolar contrast media by using
low-osmolar or iso-osmolar contrast media, (3) reducing the amount
of contrast media during PCI, (4) applying intravenously isotonic
sodium chloride solution or sodium bicarbonate solution hours
before and after PCI, and (5) avoiding use of nephrotoxic drugs
(such as nonsteroidal anti-inflammatory drugs, aminoglycosides
antibiotics, etc.). (See Stevens 1999, Schweiger 2007, Solomon
2010.) However, none of these strategies have proven to be
consistently effective in preventing CI-AKI.
SUMMARY
[0009] One aspect of the present disclosure may provide a device
for treating or reducing the risk of AKI comprising a balloon
catheter having at least one balloon, at least one sensor
associated with the balloon, and a disturbing means associated with
the balloon, wherein the balloon with the disturbing means may
generate augmented renal blood flow to avoid renal ischemia and
also to dilute the contrast media flowing into kidneys.
[0010] Another aspect of the present disclosure may provide a
device for treating or reducing the risk of AKI comprising a
balloon catheter having at least one balloon, at least one sensor
associated with the balloon, and a position indication means,
wherein the balloon may occlude the orifice of both sides of renal
arteries after inflation while allowing blood flow through the
inflated balloon while the device is deployed inside the abdominal
aorta of a patient.
[0011] Another aspect of the present disclosure may provide a
device for treating or preventing acute kidney injury, comprising a
catheter having a plurality of balloons, said balloons when
inflated, can occlude partially or completely aortic branching
arteries, through which aorta blood flows into right and left
kidneys. The balloons may be located inside the abdominal aorta. In
some embodiments, the balloons can be inflated or deflated,
partially or completely. The balloons, when inflated, can divert
aorta blood flow from directly flowing into renal arteries and/or
occlude partially or completely aortic branching arteries, through
which aorta blood flows into right and left renal arteries. The
balloons may contact the inner wall of the abdominal aorta, without
causing damage to the inner wall of the abdominal aorta and/or not
cause blood clot formation. Radio-opaque markers near proximal and
distal ends of the balloons on the catheter may be used to guide
proper vertical location of the catheter under fluoroscopy.
Radio-opaque markers on the balloon membranes may be used to guide
proper rotational orientation and proper inflation of the balloons
inside the abdominal aorta. The inflation of balloons can be
synchronized in chronological sequence with the injection of
contrast media by a physician during a cardiac catheterization
procedure. The inflation of balloons may be maintained for any
given period of time (e.g., five seconds), to allow aorta blood
with high concentrated contrast media flowing from supra-renal
aorta to infra-renal aorta, without directly flowing into renal
arteries. The endovascular catheter can have a central conduit,
which allows a guidewire passing through and or allows a coronary
catheter passing through.
[0012] Another aspect of the present disclosure may provide a
device for treating or reducing the risk of CI-AKI comprising a
catheter, a position indication means on the catheter, and a flow
disturbing means retractable into the catheter, wherein the flow
disturbing means may be positioned at the suprarenal aorta of a
patient to provide blood flow disturbance to dilute a contrast
media before being taken up by the renal arteries.
[0013] Another aspect of the present disclosure may provide a
method for treating or reducing the risk of CI-AKI comprising
inserting a catheter as described above into abdominal aorta,
placing the catheter at the suprarenal aorta, and deploying the
disturbing means at a position which may allow the disturbing means
to provide blood flow disturbance and dilute a contrast media
before the contrast media is taken into the renal arteries. In many
embodiments, the AKI comprises CI-AKI. In some embodiments, the
device may comprise a balloon catheter having a first balloon, a
second balloon, and at least one sensor associated with the first
balloon. In some embodiments, the device may comprise a balloon
catheter having a first balloon, a second balloon, and at least one
sensor associated with the second balloon. In some embodiments, the
device may further comprise a side aperture for infusing normal
saline or medication. The medication infused via the side aperture
may be a vasodilatory agent, for example, fenoldopam.
[0014] In many embodiments, the sensor may be a pressure sensor. In
certain embodiments, the pressure sensor may measure the blood flow
pressure. In some embodiments, the sensor may be a size measuring
sensor. In some embodiments, the size measuring sensor may measure
the size of balloon. In some embodiments, the device may comprise
two sensors. In some embodiments, the device may comprise a first
sensor at an upper side of the first balloon and a second sensor at
a lower side of the first balloon. In some embodiments, the device
may comprise a first sensor at an upper side of the second balloon
and a second sensor at a lower side of the second balloon. In some
embodiments, the sensor may provide data to the control unit to
control the size of the first and/or second balloons.
[0015] In many embodiments, the balloon catheter may further
include a guidewire and a spinning propeller. In some embodiments,
the spinning propeller may spin around the central guidewire to
generate directional augmented renal artery blood flow toward the
kidney. In some embodiments, the spinning propeller may be wing
shape or fin shape. In some embodiments, the device may further
comprise an additional catheter comprising a guidewire and a
spinning propeller to generate directional augmented blood flow to
the other kidney. In some embodiments, the additional catheter
comprising a spinning propeller may function either independent of
or simultaneously with the balloon catheter to generate directional
augmented blood flow to each side of kidney.
[0016] In another aspect of the present disclosure, a method for
treating CI-AKI may be provided. The method may comprise steps
of:
[0017] inserting the device comprising a balloon catheter having a
first balloon, a second balloon, and at least one sensor into
abdominal aorta;
[0018] placing the balloon catheter at a position which may allow
the first balloon to be located at the supra-renal aorta near the
orifices of bilateral renal arteries;
[0019] inflating the first balloon to occlude the orifice of both
sides of renal arteries during the application of contrast
media;
[0020] deflating the first balloon after the contrast media has
been completely employed;
[0021] inflating the second balloon to an extent so as not to
completely occlude aortic blood flow of the infra-renal aorta near
the orifices of the renal arteries;
[0022] deflating the second balloon;
[0023] and infusing normal saline and/or suitable medication via
the side aperture into the supra-renal aorta.
[0024] In many embodiments, insertion of the device into the
abdominal aorta may be applied either by a trans-femoral artery
approach, a trans-brachial artery approach, or by a trans-radial
artery approach. In some embodiments, the balloon catheter may
further comprise a guidewire and a spinning propeller. In some
embodiments, the method may further comprise inserting a guidewire
into a renal artery. In some embodiments, the method may further
comprise inserting a spinning propeller into a renal artery through
the guidewire. In some embodiments, the method may further comprise
spinning the spinning propeller around the central guidewire to
generate directional augmented renal artery blood flow toward the
kidney.
[0025] In some embodiments, the present disclosure may provide an
inventive device described herein for treating AKI. In certain
embodiments, the AKI is CI-AKI. In some embodiments, the device may
comprise a balloon catheter having a first balloon, a second
balloon, and at least one sensor associated with the second
balloon. In some embodiments, the device may comprise two sensors
described herein. In some embodiments, the balloon catheter may
further comprise a side aperture for infusing normal saline or
medication.
[0026] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one seal membrane, at least one wire
supporting the membranes, and at least one position indication
means, wherein the seal membrane may occlude the orifice of both
sides of renal arteries after deployment while also allowing blood
flow through the tunnel membrane during application of the device
inside the abdominal aorta. In some embodiments, the device may
comprise a donut-like (i.e., torus-shaped) balloon to deploy the
seal membrane upon inflation. In some embodiments, the donut-like
balloon may further comprise a side aperture for infusing normal
saline or medication, for example a diuretic. In some embodiments,
the seal membrane may not completely occlude the renal arteries
while infusion of normal saline dilutes the contrast agent in the
blood flowing into renal arteries. In some embodiments, the balloon
may be inflated by disturbing the saline infusion pressure when
contrast agent passes through the abdominal aorta.
[0027] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one wire supporting the tunnel
membrane, at least one balloon, and at least one position
indication means, wherein the balloon may occlude the orifices of
both sides of the renal arteries after deployment while still
allowing blood flow through the tunnel membrane during application
of the device inside the abdominal aorta. In some embodiments, the
balloon may have a donut-like (i.e., torus) shape to occlude the
orifices of both sides of renal arteries upon inflation. In some
embodiments, the balloon may further comprise a side aperture for
infusing normal saline or medication, for example a diuretic. In
some embodiments, the balloon may not completely occlude the renal
arteries while the normal saline infusion dilutes the contrast
agent in the blood flowing into the renal arteries. In some
embodiments, the balloon may be inflated by disturbing the saline
infusion pressure when contrast agent passes through the abdominal
aorta.
[0028] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one wire supporting the membrane, at
least one infusion tube, and at least one position indication
means, wherein the tunnel membrane may disturb blood flow to
prevent blood from directly flowing from the supra-renal aorta into
the renal arteries during application of the device inside the
abdominal aorta of a patient. In some embodiments, the at least one
infusion tube may further comprise a side aperture for infusing
normal saline or medication, for example a diuretic. In some
embodiments, infusion of normal saline may dilute the contrast
agent in the blood flowing into renal arteries. In some
embodiments, the normal saline infusion may be further increased by
disturbing the infusion pressure when contrast agent passes through
the abdominal aorta.
[0029] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one wire supporting the tunnel
membrane, at least one infusion tube, and at least one position
indication means, wherein the tunnel membrane may disturb blood
flow to prevent blood from directly flowing from the supra-renal
aorta into the renal arteries during application of the device
inside the abdominal aorta of a patient. In some embodiments, the
infusion tube may further comprise a side aperture for infusing
normal saline or medication, for example a diuretic. In some
embodiments, the normal saline infusion may dilute the contrast
agent in the blood flowing into the renal arteries. In some
embodiments, the infusion tube may be located at the lower end of
the tunnel membrane. In some embodiments, the infusion tube may be
located at the top end of the tunnel membrane. In some embodiments,
the infusion tube may be located between the lower end and top end
of the tunnel membrane. In some embodiments, the infusion tube may
be located at the tip or the shaft of the catheter. In some
embodiments, the infusion tube may be located at a certain part of
the supporting wire. In some embodiments, the normal saline
infusion may be further increased by disturbing the infusion
pressure when contrast agent passes through the abdominal
aorta.
[0030] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one wire supporting the tunnel
membrane, at least one infusion tube, and at least one position
indication means, wherein the tunnel membrane may disturb blood
flow to prevent blood from directly flowing from the supra-renal
aorta into the renal arteries during application of the device
inside the abdominal aorta of a patient. In some embodiments,
mediation may be infused near or around the upper end of the tunnel
membrane to prevent blood clot formation. In certain embodiments,
the medication may be normal saline. In some embodiments, the
infusion may be outside of the tunnel membrane. In some
embodiments, anticoagulation medication, for example heparin, may
be on the surface of tunnel membrane. The heparin may prevent blood
clot formation. In some embodiments, the device may be smooth in
contour and reduces the risk of blood clot formation.
[0031] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, at least one wire supporting the tunnel
membrane, a blood flow diversion means in conjunction with the
tunnel membrane, at least one infusion tube, and at least one
position indication means, wherein the tunnel membrane may disturb
blood flow to prevent blood from directly flowing from supra-renal
aorta into renal arteries and the blood flow diversion means may
further disturb blood flow to make the blood flow from the
infra-renal aorta into the renal arteries during application of the
device inside the abdominal aorta of the patient. In some
embodiments, the blood flow diversion means may be size adjustable.
In some embodiments, the blood flow diversion means may be shape
adjustable. In some embodiments, the blood flow diversion means may
alter blood flow from the infra-renal aorta into the renal arteries
by changing size or shape, or by other methods. In some
embodiments, the change in size or shape can be controlled with
certain timing. In some embodiments, the change in size or shape
may be in a fixed or adjustable chronological timing sequence with
the injection of contrast agent. In some embodiments, the blood
flow diversion means may increase in size inside abdominal aorta
and further reduce blood from flowing from the infra-renal aorta
into the renal arteries during application of the device inside the
abdominal aorta of a patient. In some embodiments, the blood flow
diversion means may decrease in size inside the abdominal aorta and
further allow the blood to flow from the infra-renal aorta into the
renal arteries during application of the device inside the
abdominal aorta. In some embodiments, the blood flow diversion
means may be a balloon that can inflate or deflate. In some
embodiments, the inflation-deflation balloon may be a donut-like
balloon on the outside of tunnel membrane. In some embodiments, the
inflation-deflation balloon can, when fully inflated, transiently
(for example, for five seconds) occupy a part or a whole
cross-sectional area between the tunnel membrane and the inner wall
of the abdominal aorta. In some embodiments, the
inflation-deflation balloon can, when fully inflated, transiently
occupy the cross sectional area outside the tunnel membrane and
further reduce blood flow from the infra-renal aorta into the renal
arteries. In some embodiments, the blood flow diversion means may
change its shape to reduce or to allow blood to flow from the
infra-renal aorta into the renal arteries. In some embodiments, the
blood diversion means may exert its function in the form of an
umbrella. In some embodiments, the open or close of the umbrella
may be controlled by hinges or flexure joints in conjunction with
the tunnel membrane. In some embodiments, the blood flow diversion
means may further comprise a side aperture for infusing normal
saline or medication. In some embodiments, the infusion tube may
further comprise a side aperture for infusing normal saline or
medication. In some embodiments, the medication may be diuretic. In
some embodiments, the normal saline infusion may dilute the
contrast agent in the blood flowing into the renal arteries. In
some embodiments, the normal saline infusion may be further
increased by disturbing the infusion pressure when contrast agent
passes through the abdominal aorta.
[0032] Another aspect of the present disclosure may provide a
device for treating or preventing AKI comprising a catheter having
a tunnel membrane, a sealing portion of the tunnel membrane at the
supra-renal aorta in contact with the supra-renal aorta inner wall,
at least one wire supporting the tunnel membrane, at least one
infusion tube, and at least one position indication means, wherein
the tunnel membrane may disturb blood flow to prevent blood from
directly flowing from the supra-renal aorta into the renal arteries
during application of the device inside the abdominal aorta of a
patient. In some embodiments, the sealing portion of the tunnel
membrane may be a donut-like circular balloon in contact with the
inner wall of the supra-renal aorta. In some embodiments, the
balloon may be foldable at initial status. In some embodiments, the
sealing portion of the tunnel membrane may be comprised of
biocompatible polymer, wherein the sealing portion is expandable
circumferentially from a small circle to a large circle. In some
embodiments, there may be an internal fluid-filling chamber inside
the sealing portion of the tunnel membrane and a filling fluid as a
driving force to expand the sealing portion from a small circle to
a large circle. In some embodiments, the sealing portion of the
tunnel membrane can prevent inadvertent trauma to the abdominal
aorta.
[0033] Another aspect of the present disclosure may provide a
device for synchronized injection of a contrast agent and
medications during treatment of prevention of AKI comprising an
injector containing a contrast agent chamber and a medications
chamber, two outlets for the contrast agent and the medications,
respectively, and a common injection actuator operated either by a
physician's hand or by a motor. In some embodiments, the medication
may be normal saline. In some embodiments, the container may
contain both of a contrast agent syringe and a normal saline bag,
bottle, or syringe. In some embodiments, the injection actuator may
inject contrast agent and normal saline simultaneously. In some
embodiments, the proportional amount of injected contrast agent
relative to normal saline can be adjusted by adjusting relative
diameters or relative dimensions of the syringes to control the
flow rate. In some embodiments, the injected medications may be
returned to the injection device. In certain embodiments, the
injected medications may be released near the entrance of the renal
arteries. In some embodiments, the injection outlet of normal
saline may be further connected to a volume reservoir bag or volume
reservoir balloon and may thereby generate a time difference
between actual arrival time of contrast agent and actual arrival
time of normal saline inside human body.
[0034] Another aspect of the present disclosure may provide a
device for balanced fluid flow in and outside a human body
comprising a box containing fluids or fluid conduits inflow into
and outflow outside of a human body. In some embodiments, the box
may contain two chambers in a single container that preserves total
volume of the inflow and outflow fluids. In some embodiments, the
box may have a fixed total volume, for example having a metal or
plastic shell. In some embodiments, there may be a pump for pumping
inflow and/or outflow fluids. In some embodiments, there may be
pressure transmission fluid between inflow fluid bag and outflow
fluid bag, so that the increase of outflow fluid bag pressure may
generate compression pressure to drive the inflow of inflow fluid
into the human body in the same volume. In some embodiments, there
may be fine measures of volume amounts of the inflow and outflow
fluids. In some embodiments, the box may have a combined dual
cassette that may contain two plastic tube channels (e.g., one
normal saline infusion channel and a urine outflow channel). The
combined dual cassettes may generate volume-out as volume-in
increases, the volume of the volume-out matching the volume of the
volume-in. In some embodiments, the flexible urine container (e.g.,
a bag) and the flexible saline container (e.g., a bag) may be
placed in a concealed enclosure, in which the total volume of urine
and saline remains constant. In some embodiments, the concealed
enclosure may be filled with liquid after urine and saline
containers are placed inside. The urine, the saline, and the
back-fill liquid in the enclosure may be isolated from on another
at all times. During use, an increment of urine may trigger the
injection of the same volume of saline/medication. In some
embodiments, a pump may be included to introduce energy to the
saline injection.
[0035] Another aspect of the present disclosure may provide a
device for treating or preventing CI-AKI comprising an
intra-arterial catheter comprising a tunnel membrane, one or more
balloons at each of the proximal and distal ends of the tunnel
membrane, at least one infusion tube infusing fluid into or out of
the balloons, at least one position indication means, at least one
aperture on tunnel membrane, and a wire surrounding the aperture
which controls the opening of the aperture, wherein the tunnel
membrane may disturb blood flow to prevent blood from directly
flowing from the supra-renal aorta into the renal arteries and
wherein the aperture on tunnel membrane may further allow or
prevent blood flowing from the space inside tunnel membrane to the
space outside tunnel membrane. In some embodiments, when infused
with fluid the distal balloon may be in contact with the inner wall
of the supra-renal aorta. In some embodiments, the proximal
balloon, when infused with fluid, may be in contact with the inner
wall of the infra-renal aorta. In certain embodiments, the distal
and proximal balloons may prevent inadvertent injury to the aorta
wall. In certain embodiments, the tunnel membrane may prevent blood
from directly flowing from the supra-renal aorta into the renal
arteries.
[0036] Another aspect of the present disclosure may provide a
device for treating or preventing CI-AKI comprising an
intra-arterial catheter comprising a tunnel membrane, balloons at
proximal and distal ends of tunnel membrane, at least one infusion
tube for infusing fluid into or out of the balloons, at least one
position indication means, at least one aperture on tunnel
membrane, and a wire surrounding the aperture which controls the
opening of the aperture, wherein the tunnel membrane may disturb
blood flow to prevent blood directly flowing from the supra-renal
aorta into the renal arteries and wherein the aperture on the
tunnel membrane may further allow or prevent blood flowing from the
space inside tunnel membrane to the space outside tunnel membrane.
In some embodiments, opening of aperture on the tunnel membrane may
be controlled by the wire surrounding the aperture. In some
embodiments, the number of aperture and wire sets on the tunnel
membrane may be one, two, three, four, five, six, seven, or eight
sets. In certain embodiments, the push or pull movement of the wire
may change the size of aperture on the tunnel membrane. In some
embodiments, the aperture may be closed. In some embodiments, the
aperture may be open. In some embodiments, one end of the wire may
be attached and fixed, where the other end of the wire may be
located outside of the tunnel membrane and be movable and
controlled by a physician. In some embodiments, when the wire is
pulled the wire may close the aperture such that blood cannot flow
through the aperture across the tunnel membrane. In some
embodiments, when the wire is not being pulled, the wire may allow
opening of the aperture on the tunnel membrane such that blood flow
may occur through the aperture across the tunnel membrane. In some
embodiments, the pulling movement may be synchronized with the
injection of contrast media by the physician.
[0037] Another aspect of the present disclosure may provide a
device for treating or preventing CI-AKI comprising an
intra-arterial catheter comprising a tunnel membrane, balloons at
proximal and distal ends of tunnel membrane, at least one infusion
tube infusing fluid into or out of the balloons, at least one
position indication means, at least one aperture on tunnel
membrane, and a wire surrounding the aperture which controls the
opening of the aperture, wherein the tunnel membrane may disturb
blood flow to prevent blood from directly flowing from the
supra-renal aorta into the renal arteries and wherein the aperture
on tunnel membrane may further allow or prevent blood flowing from
the space inside the tunnel membrane to the space outside the
tunnel membrane. In some embodiments, at least one infusion tube
may infuse fluid into or out of the balloons. In some embodiments,
the infusion tube may infuse fluid into the proximal and distal
balloons of the tunnel membrane. In some embodiments, the infusion
tube may aspirate fluid out of the proximal and distal balloons of
the tunnel membrane. In some embodiments, there may be one, three,
five, seven, nine, or eleven infusion tubes. In some embodiments,
there may be two, four, six, eight, ten, or twelve infusion tubes.
In some embodiments, the infusion tube may be made of plastic
material. In some embodiments, the infusion tube may be made of
Nitinol with shape-memory function such that opening of the inlet
of the tunnel membrane at the distal end is facilitated by the
shape-memory Nitinol infusion tube.
[0038] Another aspect of the present disclosure may provide a
device for treating or preventing CI-AKI comprising a catheter
comprising a tunnel membrane, balloons at proximal and distal ends
of the tunnel membrane, at least one infusion tube infusing fluid
into or out of the balloons, at least one position indication
means, at least one aperture on tunnel membrane, and the opening of
the aperture controlled by a wire surrounding the aperture, wherein
the tunnel membrane may disturb blood flow to prevent blood from
directly flowing from the supra-renal aorta into the renal arteries
and wherein the aperture on tunnel membrane can further allow or
prevent blood flowing from the space inside the tunnel membrane to
the space outside the tunnel membrane. In some embodiments, the
position indication means may be radio-opaque markers. In some
embodiments, the radio-opaque markers may help the physician
position the device at proper horizontal level and at proper
front-rear level inside the abdominal aorta of a patient.
[0039] Another aspect of the present disclosure may provide a
device for treating or preventing AKI, for example CI-AKI,
comprising an expandable mesh braid having a low-profile
configuration for delivery through the vasculature and an expanded
configuration for occluding the renal arteries, and a catheter
shaft assembly. The catheter shaft assembly may be actuated to
deploy an occlusive element, for example the expandable mesh braid,
to occlude the renal arteries during injection of contrast media or
other harmful substance. The catheter shaft assembly may comprise
one or more of an inner shaft, an outer shaft, and a cover. The
distal end of the expandable mesh braid may be coupled to the inner
shaft while the proximal end of the expandable mesh braid may be
coupled to the outer shaft such that translation of the inner shaft
relative to the outer shaft deploys or collapses the expandable
mesh braid. The device may further comprise a time-delayed release
mechanism configured to automatically collapse the expandable mesh
braid after a pre-determined amount of time following
deployment.
[0040] Another aspect of the present disclosure may provide a
device for treating or preventing acute kidney injury, comprising a
catheter having a plurality of balloons, when inflated, can occlude
partially or completely aortic branching arteries, through which
aorta blood flows into right and left kidneys. In some embodiments,
the acute kidney injury may be contrast induced nephropathy or
contrast-induced acute kidney injury. In some embodiments, the
balloons may be located inside the abdominal aorta. In some
embodiments, the balloons can be inflated or deflated. In some
embodiments, the balloons can be inflated by fluid or gas. In some
embodiments, the balloons can be inflated or deflated partially or
completely. In some embodiments, the balloons, when inflated, can
divert aorta blood flow from directly flowing into renal arteries.
In some embodiments, the balloons, when inflated, can occlude
partially or completely aortic branching arteries, through which
aorta blood flows into right and left kidneys. In some embodiments,
the aortic branching arteries may include right and left renal
arteries. In some embodiments, the balloons may contact with inner
wall of the abdominal aorta. In some embodiments, the contact of
the balloons with inner wall of the abdominal aorta may not cause
damage to the inner wall of the abdominal aorta. In some
embodiments, the balloons may not cause blood clot formation. In
some embodiments, there may be radio-opaque markers near proximal
and distal ends of the balloons on the catheter to guide proper
vertical location of the catheter under fluoroscopy. In some
embodiments, there may be radio-opaque markers on the balloon
membrane to guide proper rotational orientation and proper
inflation of the balloons inside the abdominal aorta. In some
embodiments, the proper rotational orientation can be guided by
overlapping of front and rear radio-opaque linear markers under
fluoroscopy. In some embodiments, the proper inflation can be
guided by flattening of lateral radio-opaque curve markers under
fluoroscopy. In some embodiments, the inflation of balloons can be
synchronized in chronological sequence with the injection of
contrast media by a physician during a cardiac catheterization
procedure. In some embodiments, the inflation of balloons may be
maintained for a certain period of time, for example five seconds,
to allow aorta blood with high concentrated contrast media flowing
from supra-renal aorta to infra-renal aorta, without directly
flowing into renal arteries. In some embodiments, the endovascular
catheter may have a central conduit. In some embodiments, the
central conduit can allow a guidewire passing through. In some
embodiments, the central conduit can allow a coronary catheter
passing through. In some embodiments, the endovascular catheter may
be a variant of introducer and can be used as an introducer sheath.
In some embodiments, the endovascular catheter may be used as a
standalone device. For example, a different catheter may be
introduced into the patient via a trans-femoral or trans-radial
route, the renal ostia shielding catheter may be inserted via a
different trans-femoral route. Inside the abdominal aorta, the
shielding catheter may be advanced to be substantially parallel
with the different catheter, without interfering with its function
even when the occlude element(s) of the shielding catheter are
deployed.
[0041] Aspects of the present disclosure may provide a device for
preventing acute kidney injury from contrast agent introduced into
vasculature of a subject. The device may comprise a catheter shaft
comprising proximal portion and a distal portion, an occlusive
element disposed on the proximal portion, and one or more position
indication feature disposed on one or more of the catheter shaft or
the occlusive element. The occlusive element may have an expanded
configuration in which, when advanced into an abdominal aorta and
positioned adjacent renal artery ostia of the subject, is sized to
occlude the renal artery ostia while allowing blood flow over the
catheter shaft. The distal portion may be configured to remain
outside a body of the subject when the proximal portion is
positioned adjacent renal artery ostia of the subject.
[0042] The occlusive element may comprise a first expandable member
disposed on a first lateral side of the proximal portion and a
second expandable member disposed on a second lateral side of the
proximal portion. The first and second expandable members may have
an expanded configuration in which, when advanced into an abdominal
aorta and positioned adjacent renal artery ostia of the subject,
are sized to occlude the renal artery ostia while allowing blood
flow over the catheter shaft. The first expandable member and the
second expandable member may be in fluid communication with one
another. For example, the first expandable member and the second
expandable member may comprise a single balloon, and the single
balloon may be configured to assume a predetermined, desired shape
when expanded. Alternatively, the first expandable member and the
second expandable member may be fluidly independent of one another.
For example, the first expandable member comprises a first balloon
and the second expandable member comprises a second balloon, and
the first and second balloons may be configured to assume
predetermined, desired shapes when expanded. The expanded
configuration of the occlusive element may be spherical,
ellipsoidal, cylindrical, an n-sided prism, conical, pyramidal,
butterfly-shaped, dumbbell-shaped, cigar-shaped, torpedo-shaped, or
submarine-shaped.
[0043] The one or more position indication features may be disposed
on the proximal portion of the catheter shaft adjacent the
occlusive element. Alternatively or in combination, the one or more
position indication features may be disposed on the occlusive
element. The position indication feature(s) may comprise one or
more radio-opaque markers. The radio-opaque marker(s) comprises one
or more radio-opaque longitudinal marker. The radio-opaque
longitudinal marker(s) may comprise a plurality of radio-opaque
longitudinal markers disposed on the occlusive element along a
longitudinal axis of the occlusive element.
[0044] The device may further comprise an orientation element
disposed on the distal portion of the catheter shaft. The
orientation element may be aligned with the occlusive element and
configured to indicate the orientation of the occlusive element
when positioned adjacent renal artery ostia of the subject. The
orientation element may comprise one or more of a visible marking,
a protrusion, a wing, or a flag, for example.
[0045] Aspects of the present disclosure may provide a system for
preventing acute kidney injury from contrast agent introduced into
vasculature of a subject. The device may comprise a catheter shaft
comprising proximal portion and a distal portion, an occlusive
element disposed on the proximal portion, and a time-delayed
release mechanism in communication with the occlusive element. The
occlusive element may have an expanded configuration in which, when
advanced into an abdominal aorta and positioned adjacent renal
artery ostia of the subject, is sized to occlude the renal artery
ostia while allowing blood flow over the catheter shaft. The distal
portion may be configured to remain outside a body of the subject
when the proximal portion is positioned adjacent renal artery ostia
of the subject. The time-delayed release mechanism may be
configured to collapse the occlusive element after a pre-determined
amount of time following expansion of the occlusive element.
[0046] The time-delayed release mechanism may comprise an energy
accumulation and storage component. The energy accumulation and
storage component may comprise a spring. The energy accumulation
and storage component may comprise a syringe comprising a plunger,
and the spring may be coupled to the plunger.
[0047] The one or more position indication features may be disposed
on one or more of the catheter shaft or the occlusive element. The
position indication feature(s) may be disposed on the proximal
portion of the catheter shaft adjacent the occlusive element. The
position indication feature(s) may be disposed on the occlusive
element. The position indication feature(s) may comprise one or
more radio-opaque marker. The radio-opaque marker(s) may comprise
one or more radio-opaque longitudinal marker. The radio-opaque
longitudinal marker(s) may comprise a plurality of radio-opaque
longitudinal markers disposed on the occlusive element along a
longitudinal axis of the occlusive element.
[0048] The occlusive element may comprise a mesh braid. The
occlusive element may comprise an expandable member. The expandable
member may comprise an inflatable balloon. The occlusive element
may comprise a first expandable member disposed on a first lateral
side of the proximal portion and a second expandable member
disposed on a second lateral side of the proximal portion. The
first and second expandable members may have an expanded
configuration in which when advanced into an abdominal aorta and
positioned adjacent renal artery ostia of the subject are sized to
occlude the renal artery ostia while allowing blood flow over the
catheter shaft. The first expandable member and the second
expandable member may be in fluid communication with one another.
Alternatively, the first expandable member and the second
expandable member may be fluidly independent of one another. The
expanded configuration of the occlusive element may be spherical,
ellipsoidal, cylindrical, an n-sided prism, conical, pyramidal,
butterfly-shaped, dumbbell-shaped, cigar-shaped, torpedo-shaped, or
submarine-shaped.
[0049] The system may further comprise an orientation element
disposed on the distal portion of the catheter shaft. The
orientation element may be aligned with the occlusive element and
configured to indicate the orientation of the occlusive element
when positioned adjacent renal artery ostia of the subject. The
orientation element may comprise one or more of a visible marking,
a protrusion, a wing, or a flag, for example.
[0050] Aspects of the present disclosure may provide a method of
preventing acute kidney injury from contrast agent introduced into
vasculature of a subject. A proximal portion of a catheter device
comprising a catheter shaft and an occlusive element may be
positioned in an abdominal aorta of the subject adjacent renal
artery ostia of the subject. One or more position indication
feature disposed on one or more of the catheter shaft or the
occlusive element may be observed to verify a correct placement
and/or orientation of the catheter shaft and the occlusive element.
The occlusive element of the catheter device may be deployed to
occlude the renal artery ostia. A bolus of the contrast agent may
then be introduced into the abdominal aorta of the subject while
the occlusive element is deployed to occlude the renal artery
ostia, thereby preventing the contrast agent from entering into
renal arteries of the subject. The occlusive element may be
collapsed after the bolus of the contrast agent has been
introduced, thereby allowing blood flow to the renal arteries to
resume.
[0051] In positioning the proximal portion of the catheter device,
a position of the one or more position indication features may be
observed and the proximal portion of the catheter device may be
positioned in response to the observed position. The indication
feature(s) may comprise a radio-opaque marker, and the position
indication feature(s) may be observed using x-ray imaging.
[0052] The occlusion of the renal artery ostia may be confirmed
when the occlusive element is deployed. For instance, the position
indication feature(s) may comprise one or more radio-opaque
longitudinal markers, and confirming occlusion of the renal artery
ostia may be confirmed by observing the appearance of a bowed
section in the one or more radio-opaque longitudinal markers using
x-ray imaging. When the occlusive element is deployed, a portion of
the occlusive element may bow into the renal artery ostia and the
radio-opaque longitudinal markers may bow to allow this bowing to
be observed.
[0053] In positioning the proximal portion of the catheter device,
an orientation of an orientation element disposed on a distal
portion of the catheter device may be observed and the proximal
portion of the catheter device may be positioned in response to the
observed orientation. The orientation element may be aligned with
the occlusive element and configured to indicate the orientation of
the occlusive element when positioned adjacent renal artery ostia
of the subject.
[0054] The occlusive element may comprise an expandable mesh braid,
and the occlusive element may be deployed by expanding the
expandable mesh braid and collapsed by collapsing the expandable
mesh braid.
[0055] The occlusive element may comprise an expandable member, and
the occlusive element may be expanded by expanding the expandable
member and collapsed by collapsing the expandable member.
[0056] The expandable member may comprise an inflatable balloon,
and the expandable member may be expanded by inflating the balloon
and collapsed by deflating the balloon.
[0057] The occlusive element may comprise a first expandable member
disposed on a first lateral side of the proximal portion and a
second expandable member disposed on a second lateral side of the
proximal portion, wherein deploying the occlusive element comprises
expanding the first and second expandable members, and wherein
collapsing the occlusive element comprises collapsing the first and
second expandable members.
[0058] The first and second expandable members may be expanded
independently of one another. Alternatively, the first and second
expandable members may be simultaneously expanded.
[0059] The occlusive element may be collapsed after a
pre-determined amount of time. The deployment of the occlusive
element and introduction of the bolus of the contrast agent may be
synchronized.
[0060] Additional aspects and advantages of the present disclosure
will become readily apparent to those skilled in this art from the
following detailed description, wherein only illustrative
embodiments of the present disclosure are shown and described. As
will be realized, the present disclosure is capable of other and
different embodiments, and its several details are capable of
modifications in various obvious respects, all without departing
from the disclosure. Accordingly, the drawings and description are
to be regarded as illustrative in nature, and not as
restrictive.
INCORPORATION BY REFERENCE
[0061] All publications, patents, and patent applications mentioned
in this specification are herein incorporated by reference to the
same extent as if each individual publication, patent, or patent
application was specifically and individually indicated to be
incorporated by reference. To the extent publications and patents
or patent applications incorporated by reference contradict the
disclosure contained in the specification, the specification is
intended to supersede and/or take precedence over any such
contradictory material.
BRIEF DESCRIPTION OF THE DRAWINGS
[0062] The novel features of the invention are set forth with
particularity in the appended claims. A better understanding of the
features and advantages of the present disclosure will be obtained
by reference to the following detailed description that sets forth
illustrative embodiments, in which the principles of the invention
are utilized, and the accompanying drawings (also "Figure" and
"FIG." herein), of which:
[0063] FIG. 1 illustrates an embodiment of a device comprising a
balloon catheter having a first balloon positioned in the
supra-renal aorta near the orifices of the bilateral renal arteries
for treating AKI.
[0064] FIG. 2 shows the embodiment illustrated in FIG. 1, wherein
the first balloon is inflated to occlude the orifices of both sides
of the renal arteries.
[0065] FIGS. 3A-3D are perspective views of the first balloon of
the embodiment of FIG. 1. FIG. 3A shows a cylinder-like inflated
balloon. FIG. 3B shows a cross-section view of the cylinder-like
inflated balloon of FIG. 3A. FIG. 3C shows the morphology of an
exemplary inflated first balloon which is "butterfly-like". FIG. 3D
shows a cross-section view of the butterfly-like inflated balloon
of FIG. 3C.
[0066] FIG. 4 shows an embodiment with a deflated first balloon and
an inflated second balloon at the location of the infra-renal aorta
near the orifices of the renal arteries.
[0067] FIG. 5 shows the vortex blood flow caused by distension of
the second balloon.
[0068] FIG. 6 shows infusion of normal saline from a control box,
through a catheter pore, and into the abdominal aorta while the
second balloon remains inflated.
[0069] FIG. 7 shows another aspect of the present disclosure where
renal artery blood flow augmentation is exerted by periodic
inflation and deflation of the first balloon.
[0070] FIG. 8 shows an embodiment of the device at the end of PCI
wherein both the first and second balloons have been deflated and a
continuous infusion of normal saline is applied for post-procedural
hydration.
[0071] FIG. 9 shows another aspect of the present disclosure
wherein a guidewire is used to guide the device for insertion into
the renal artery.
[0072] FIG. 10 shows an embodiment with a spinning propeller
inserted into renal artery which spins around the central guidewire
in order to augment renal artery blood flow toward the kidney.
[0073] FIGS. 11A-11B show alternative embodiments of a spinning
propeller.
[0074] FIG. 12 illustrates an exemplary balloon-type acoustic wave
pump at work.
[0075] FIGS. 13A-13B show how the exemplary acoustic wave pump
works via the inflation and deflation of the balloon.
[0076] FIGS. 14A-14B illustrate yet another embodiment of the
present disclosure wherein the device comprises a first balloon
inflated to a pre-determined size and a second balloon around the
first balloon. An acoustic wave may be generated by the second
balloon.
[0077] FIGS. 15A-15B show computer-generated blood flow simulation
diagrams without (FIG. 15A) and with (FIG. 15B) a first balloon
attached to a tunnel membrane. The curved lines represent the
streamlines.
[0078] FIGS. 16A-16D show another aspect of the present disclosure
wherein a disturbing means is extended toward the infra-renal aorta
to further confine the renal arteries to intake blood from the
infra-renal aorta. FIG. 16A shows an embodiment wherein the
disturbing means is a tunnel membrane. FIG. 16B shows a
cross-sectional top-down view of the embodiment of FIG. 16A. FIG.
16C shows an embodiment with an umbrella-like device used as an
anchor to facilitate deployment of the tunnel membrane. FIG. 16D
shows an embodiment with a smaller second balloon used as an anchor
to facilitate deployment of the tunnel membrane.
[0079] FIGS. 17A-17C shows another embodiment of a disturbing means
comprising a cone-shaped wire device partially covered by the
tunnel membrane. FIG. 17A shows a cross-sectional side-view of an
exemplary wire device. FIG. 17B shows the specification of the
embodiment of FIG. 17A in the aorta. FIG. 17C shows the application
of normal saline or other suitable medicines via at least one
injection hole.
[0080] FIGS. 18A-18D illustrate another embodiment of a disturbing
means comprising a cone-shaped wire device partially covered with
the tunnel membrane. FIG. 18A shows a cross-sectional side-view of
the embodiment. FIG. 18B shows a top view of the embodiment. FIG.
18C shows a bottom view of the embodiment. FIG. 18D provides an
isometric view of the embodiment.
[0081] FIGS. 19A-19C illustrate the deployment of an embodiment of
a catheter device to treat or prevent AKI. FIG. 19A shows the
device with the tunnel membrane at the beginning of deployment from
the catheter. FIG. 19B shows the tunnel membrane partially deployed
into the abdominal aorta. FIG. 19C shows the tunnel membrane fully
deployed into the abdominal aorta.
[0082] FIGS. 20A-20D illustrate another embodiment of a device for
treating or preventing AKI. FIG. 20A shows a device comprising a
catheter with a tunnel membrane, a seal membrane, multiple
supporting wires, and one donut-like balloon. FIG. 20B shows the
device with the donut-like balloon in its deflated state. FIG. 20A
shows the device with the donut-like balloon in its inflated state.
FIG. 20D shows the device positioned inside the abdominal aorta
with the balloon inflated to deploy the seal membrane and occlude
the orifices of both sides of the renal arteries.
[0083] FIGS. 21A-21C illustrate another embodiment of the present
disclosure comprising a catheter with a tunnel membrane, multiple
supporting wires, and a donut-like balloon. FIG. 21A shows the
embodiment with the donut-like balloon in its deflated state. FIG.
21B shows the embodiment with the donut-like balloon in its
inflated state. FIG. 21C shows the embodiment positioned inside
abdominal aorta with the balloon inflated to occlude the orifices
of both sides of the renal arteries.
[0084] FIGS. 22A-22B illustrate yet another embodiment of the
present disclosure. FIG. 22A shows an embodiment comprising a
catheter having a tunnel membrane, multiple supporting wires, one
infusion tube at the lower end of the tunnel membrane, and one
infusion tube attached to the tunnel membrane. FIG. 22B shows the
embodiment of FIG. 22A positioned inside the abdominal aorta.
[0085] FIG. 23 illustrates still another embodiment of the present
disclosure. The device shown comprises a catheter having a tunnel
membrane, a donut-like balloon in the supra-renal aorta near the
orifices of the bilateral renal arteries, a donut-like balloon in
the infra-renal aorta near the orifices of the bilateral renal
arteries, three position indication means, two infusion tubes for
infusing fluid into or out of the balloons, two apertures on the
tunnel membrane, and a wire surrounding the apertures.
[0086] FIGS. 24A-24B illustrate an exemplary device for
synchronized injection of contrast agent and medications in
treating or preventing AKI. FIG. 24A shows a synchronized injector
of contrast agent and medication which allows for adjustment of the
relative amount and relative time to arrival inside human body of
the two fluids. FIG. 24B shows how the device may enable
chronological and volumetric differences between the two
fluids.
[0087] FIG. 25 illustrates an embodiment of a device for balancing
fluid flow in and out of a human body. The device shown comprises a
box containing fluids or fluid conduits to allow inflow into and
outflow out of the human body.
[0088] FIGS. 26A-26C show yet another embodiment of the present
disclosure. FIG. 26A shows a catheter shaft comprising an outer
shaft, an inner shaft disposed therein. FIG. 26B shows the catheter
shaft device with expandable mesh braid coupled to the inner and
outer shafts in a low-profile configuration. FIG. 26C shows the
catheter shaft device with expandable mesh braid in an expanded
configuration.
[0089] FIGS. 26D-26G show further embodiments of the present
disclosure. FIG. 26D shows a prototype of a catheter shaft device
with expandable mesh braid. FIG. 26E shows a fully open mesh braid.
FIG. 26F shows a partially collapsed mesh braid. FIG. 26G shows a
fully collapsed mesh braid.
[0090] FIGS. 27A-27D show the deployment of the embodiment of FIGS.
26A-26G. FIG. 27A shows the insertion of the embodiment into the
abdominal aorta. FIG. 27B shows the positioning of the device in
the abdominal aorta. FIG. 27C shows the device deployed. FIG. 27D
shows the device collapsed.
[0091] FIGS. 28A-28C show a further embodiment of the present
disclosure. FIG. 28A shows a prototype of a balloon catheter device
having two ellipsoidal balloons, one balloon for occluding each of
the left and right renal arteries, in a collapsed configuration.
FIG. 28B shows the prototype in an expanded configuration. FIG. 28C
shows the prototype in the expanded configuration inside a model
abdominal aorta.
[0092] FIGS. 29A-29D show an embodiment of a position indication
feature which can be used to determine if a balloon catheter device
occludes the renal arteries. FIGS. 29A and 29B shows an axial view
along the abdominal aorta depicting the relative positions of the
left and right balloons in the initial position (FIG. 29A) and the
"protective" or expanded position (FIG. 29B). FIGS. 29C and 29D
show the position indication feature in the initial position (FIG.
29C) and the "protected" or expanded position (FIG. 29D).
[0093] FIG. 30 shows an X-Ray of the balloon catheter of FIGS.
28A-28C inserted into a subject, with the balloons in the
"protective" position.
[0094] FIG. 31 shows an embodiment of a time-delayed release
mechanism configured to automatically collapse the occlusive
element after a pre-determined amount of time following
deployment.
[0095] FIG. 32 shows a further embodiment of the present disclosure
including the prototype of FIGS. 28A-28C and the time-delayed
release mechanism of FIG. 31.
DETAILED DESCRIPTION
[0096] While various embodiments of the invention have been shown
and described herein, it will be obvious to those skilled in the
art that such embodiments are provided by way of example only.
Numerous variations, changes, and substitutions may occur to those
skilled in the art without departing from the invention. It should
be understood that various alternatives to the embodiments of the
invention described herein may be employed.
[0097] Provided herein are devices and systems that specifically
focus on solving one or both of the two main pathophysiological
culprits of CI-AKI--prolonged transit of contrast media inside the
kidneys and renal outer medulla ischemia. In some embodiments,
devices, systems, and methods are provided for reducing contrast
media concentrations or amounts entering the renal arteries to
prevent AKI, for example CI-AKI. Alternatively or in combination,
some embodiments provide devices, systems, and methods for
augmenting blood flow towards the renal arteries that feed the
kidneys to treat or prevent renal ischemia.
[0098] In some embodiments, a device for treating AKI, for example
CI-AKI, may comprise a balloon catheter having at least a first
balloon, at least one sensor associated with the first balloon, and
at least one position indication means. The balloon catheter device
may additionally comprise a second balloon. The first balloon may,
for example, be placed inside the abdominal aorta of a patient so
as to occlude the orifices of both sides of the renal arteries
after inflation. Blood may continue to flow through the inflated
balloon during application of the device inside the abdominal
aorta. The position indication means may for example be a
radio-opaque marker, or other detectable marker, in order to
improve visibility of the device during deployment for example with
fluoroscopy or radiography.
[0099] Alternatively or in combination, the balloon catheter device
may comprise a first balloon, a second balloon, and at least one
sensor associated with one of the first or second balloons. The
sensor may for example be a pressure sensor or a size-measuring
sensor. Further, the device may comprise a plurality of sensors on
one or more of the first or second balloons. The plurality of
sensors may for example comprise one or more of a pressure sensor,
one or more of a size-measuring sensor, or any combination
thereof.
[0100] Some embodiments of the balloon catheter device may
alternatively or in combination comprise at least one side aperture
on the catheter to allow for application of normal saline or other
medications. The normal saline or other medications may be infused
from a control box through the catheter into the supra-renal aorta.
In some embodiments, the normal saline or other medications may be
applied for example via a side aperture between the first and
second balloons. Alternatively or in combination, the normal saline
or other medications may be applied for example via the tip of the
catheter.
[0101] Alternatively or in combination, the balloon catheter device
may comprise at least one guidewire and at least one spinning
propeller. The spinning propeller may for example spin around the
central guidewire in order to generate augmented renal artery blood
flow toward a first kidney. The spinning propeller may for example
be wing-shaped or fin-shaped. The balloon catheter device may
further comprise an additional guidewire and an additional spinning
propeller. The additional guidewire and additional spinning
propeller may be operated so as to generate augmented renal artery
blood flow towards a second kidney. Operation of the spinning
propeller may be functionally independent or simultaneous with
operation of the balloon catheter in order to generate directional
augmented flow toward one or both of the kidneys. Alternatively or
in combination, blood flow towards the renal arteries may be
increased using an acoustic wave pump or a micro-electro-mechanical
(MEM) micropump.
[0102] Alternatively or in combination, the balloon catheter device
may comprise a flow disturbing means associated with the first
balloon. For example, the flow disturbing means may be a tunnel
membrane attached to the first balloon and adapted to fit inside
the aorta wall. The flow disturbing means may alternatively be an
umbrella-like blood flow reducing component that may be attached to
either the catheter or the first balloon and positioned either in
the supra-renal aorta above the renal arteries or in the
infra-renal aorta below the renal arteries.
[0103] The flow disturbing means may for example be a cone-shaped
wire device that is partially covered with a tunnel membrane. The
device may be deployed from the catheter. The cone-shaped wire
device may comprise a plurality of wires, for example at least 3
wires. In some embodiments, the cone-shaped wire device may
comprise any number of wires suitable to provide a disturbing
means. The wires may for example be made of any superelastic or
pseudoeleastic material, for example nitinol. The cone-shaped wire
device may further comprise an upper cylinder portion used to form
a tight contact between the device and the aorta wall.
[0104] The flow disturbing means may alternatively be any similar
shape, structure, or function as an umbrella-like blood flow
reducing component. The flow disturbing means may be any device
that can disturb blood flow such that there may be lower blood
intake by the renal arteries from the infra-renal aorta. The flow
disturbing means may further comprise one or more injection hole
through which normal saline or other medications may be injected,
for example to dilute a contrast agent in the blood prior to being
taken up by the renal arteries towards the kidneys. In some
embodiments, the injection hole may be on the catheter, for
example, close to the catheter tip from which the disturbing means
may be deployed.
[0105] In some embodiments, a device for treating or preventing
AKI, for example CI-AKI, may comprise a catheter, a tunnel
membrane, at least one supporting wire, at least one flow
disturbing means, and at least one position indication means. When
deployed in the abdominal aorta, the flow disturbing means may
dilute a contrast agent flowing into the renal arteries while
allowing for blood to flow through the tunnel membrane. The device
may comprise a plurality of supporting wires. Alternatively or in
combination, the device may comprise an infusion tube.
[0106] Alternatively or in combination, the device may further
comprise a flow diversion means in conjunction with the tunnel
membrane. The flow diversion means may be deployed inside the
abdominal aorta such that the orifices of both sides of the renal
arteries are occluded by the flow diversion means and such that
blood is allowed to flow through the tunnel membrane. The position
indication means may for example be a radio-opaque marker, or other
detectable marker, in order to improve visibility of the device
during deployment for example with fluoroscopy or radiography.
[0107] Alternatively or in combination, the device may further
comprise at least one balloon at the proximal end of the tunnel
membrane, at least one balloon at the distal end of the tunnel
membrane, at least one infusion tube, at least one aperture on the
tunnel membrane, and a wire surrounding the aperture which controls
the opening of the aperture. The infusion tube may be used to
infuse a fluid into or out of the balloons. The device may comprise
at least two infusion tubes. The device may comprise a plurality of
apertures and wires controlling the apertures. The tunnel membrane
may disturb blood flow to prevent blood from flowing into the renal
arteries directly from the supra-renal aorta, instead shunting the
blood through the tunnel membrane into the infra-renal aorta. The
aperture on the tunnel membrane may further allow or prevent blood
to flow from the space inside the tunnel membrane to the space
outside the tunnel membrane. Shunting on the tunnel membrane may be
synchronized with injection of a contrast media by the
physician.
[0108] Alternatively, the device may comprise a catheter shaft
assembly actuated to deploy an occlusive element to occlude the
renal arteries during injection of contrast media or other harmful
substance. The catheter shaft assembly may comprise one or more of
an inner shaft, an outer shaft, and a cover. The inner shaft may be
disposed within the outer shaft and translatable relative to each
other. The occlusive element may for example be an expandable mesh
braid which may comprise a plurality of filaments. When expanded,
the expandable mesh braid may contact the inner walls of the
abdominal aorta and cover the renal artery ostia. The expanded mesh
braid may have a filament density sufficient to occlude blood flow
into or divert blood flow away from the renal ostia. In some
embodiments, the expandable mesh braid may be radially expanded and
axially compressed to increase the filament density at the axially
central region of the expanded mesh braid which covers the renal
ostia. The distal end of the expandable mesh braid may be coupled
to the inner shaft. The proximal end of the expandable mesh braid
may be coupled to the outer shaft such that translation of the
inner shaft relative to the outer shaft deploys or collapses the
expandable mesh braid. The device may further comprise a
time-delayed release mechanism configured to automatically collapse
the expandable mesh braid after a pre-determined amount of time
following deployment. The time-delayed release mechanism may be
provided on a handle or controller of the device.
[0109] In many embodiments, the device may comprise an occlusive
element. The occlusive element may comprise any of the balloons,
membranes, or expandable elements (e.g. mesh braid) described
herein. The occlusive element may be disposed on or around a
proximal portion of a catheter. The occlusive element may be
advanced into an abdominal aorta and positioned adjacent renal
ostia in a collapsed configuration. The occlusive element may then
be expanded (e.g. inflated) into an expanded configuration which is
sized to partially or fully occlude or divert blood flow from the
renal artery ostia while allowing blood flow over the catheter
shaft. It will be understood by one of ordinary skill in the art
that any of the occlusive elements (e.g. balloons, membranes,
braids, etc.) described herein or any of the features thereof may
be combined as desired in order to arrive at a device for treating
or preventing AKI. Any of the occlusive elements, or any
combination thereof, may be combined with any of the position
indication means or features, flow disturbing means or elements,
flow pumps, sensors, flow augmentation means or elements, injection
synchronizer, fluid balancer, time-delayed release mechanism, any
other element described herein, or any combination thereof, as
desired by one of ordinary skill in the art, to arrive at a device
for treating or preventing AKI.
[0110] FIG. 1 shows an exemplary embodiment of a device for
treating or preventing AKI, for example CI-AKI, comprising a
balloon catheter device. The device 100 may comprise a catheter
101, a first balloon 102, a second balloon 103, and a position
indication means, for example a radio-opaque marker, on the tip of
the catheter 101. The device 100 may be inserted into the abdominal
aorta of a patient and positioned by monitoring the position of the
radio-opaque marker for guidance. The device 100 may be inserted
into the abdominal aorta using either a trans-femoral arterial
approach, a trans-brachial artery approach, or a trans-radial
artery approach. The tip of the catheter 101, which may include a
radio-opaque marker, may be situated so as to position the first
balloon in the supra-renal aorta such that the first balloon lies
near the orifices of the bilateral renal arteries.
[0111] FIG. 2 shows the device 100 positioned in the supra-renal
aorta near the orifices of the bilateral renal arteries. The first
balloon 102 is inflated such that the balloon 102 occludes the
orifices of both sides of the renal arteries. The second balloon
103 remains un-inflated. Occlusion of the renal arteries by the
first balloon 102 may prevent a bolus influx of harmful agents, for
example a contrast media, from flowing into the renal arteries from
the supra-renal aorta. Such occlusion may reduce the toxic effects
of said harmful agents by preventing delivery of the harmful agents
to the kidney. The bolus of contrast media may be introduced using
the same device 100 or a separate device that has been introduced
either through the same or different path in the vasculature.
[0112] FIGS. 3A to 3D illustrate various embodiments of the first
balloon 102. FIG. 3A shows an inflated first balloon 102 positioned
along and circulating the catheter 101. FIG. 3B shows a
cross-sectional view of the first balloon 102 of FIG. 3A. The
balloon may be positioned around the catheter 101 such that a
hollow area is formed between the inner edge of the balloon 102 and
the catheter 101 to form a donut-like balloon shape. By providing a
hollow space inside of the balloon 102, blood may be allowed to
flow along the catheter 101 when the balloon 102 is inflated to
occlude the orifices of both sides of the renal arteries. The first
balloon 102 may be inflated via at least one connection tube 304
extending from the catheter 101 to the balloon 102. For example,
the balloon may be inflated via four connection tubes 304 as shown
in FIG. 3B. FIG. 3C shows an alternative embodiment of the first
balloon 102. The first balloon 102 may be comprised of bilateral
inflated balloon sections 303a and 303b to form a butterfly-like
balloon shape. The sections 303a and 303b may be connected to each
side of catheter 101 via at least one connection tube 304.
Inflation of the balloon sections 303a and 303b may occlude the
orifices of both sides of the renal arteries while also allowing
blood to flow along the catheter 101. FIG. 3D shows a
cross-sectional view of the butterfly-like embodiment of the first
balloon 102 depicted in FIG. 3C. The balloon sections 303a and 303b
may be connected to the catheter 101 via one or more connection
tube 304. For example, FIG. 3D depicts one connection tube per
balloon section on each side of the catheter 101. In some
embodiments, the balloon may have one, two, three, four, or five
connection tubes 304 to connect the first balloon 102 to the
catheter 101. The connection tube(s) may be used to provide
inflation or deflation of the first balloon 102.
[0113] In some embodiments, the first balloon 102 may be donut-like
after inflation. In some embodiments, the first balloon 102 may
have a butterfly-like shape after inflation.
[0114] FIG. 4 shows the device 100 with a deflated first balloon
102 and inflated second balloon 103. The first balloon 102 may be
deflated (indicated by arrows) and the second balloon 103 may be
inflated after contrast media-containing blood has passed beyond
the orifices of the renal arteries. The second balloon 103 may be
positioned in the infra-renal aorta near the orifices of the renal
arteries. The second balloon 103 may be inflated to an extent such
that is does not completely occlude aortic blood flow.
[0115] As shown in FIG. 5, distension of the inflated second
balloon 103 may generate a vortex-like pattern of blood flow.
Vortex flow may facilitate or augment renal artery blood flow. In
some embodiments, there may be at least one sensor (for example 504
or 505) associated with the first balloon 102 or second balloon 103
for the control of inflation and/or deflation of either the first
or second balloon. In some embodiments, the sensor may be a
pressure sensor to detect balloon inflation. In some embodiments,
the sensor may be a size-measuring sensor to detect the relative
size of either the first balloon or the second balloon. A
non-limiting example in shown in FIG. 5 where there is a first
pressure sensor 504 at the lower side of the first balloon or at
the upper side of the second balloon. A second pressure sensor 505
is at the lower side of the second balloon. Sensors 504 and 505 may
alternatively or in combination be one or more of a size-measuring
sensor. Sensors 504 and 505 may be associated with either one of
the first balloon 102 or second balloon 103.
[0116] Analysis of data generated by the pressure sensors can be
used for instantaneous titration of the degree of distension of the
second balloon 103 in order to provide an adequate pressure
gradient to generate vortex blood flow into the renal arteries.
Additionally, the altered aortic blood flow may increase the renal
artery blood flow due to the local proximity and diameter of the
distended second balloon 103. In some embodiments, the diameter of
the distended second balloon 103 may be adjustable such that the
diameter of the distended balloon 103 does not fully obstruct blood
flow in the aorta. By only partially obstructing blood flow, an
inadequacy of aortic blood flow at the distal aorta or at branches
of the aorta, for example the right and left common iliac arteries,
may be prevented. Furthermore, the wall of the aorta may be
preserved from injury by the balloon distension.
[0117] The device 100 may further comprise a control box 509 placed
outside of the patient. The control box may be in connection with
the balloon catheter and may serve several functions including any
of the following: inflation of the first and second balloons,
deflation of the first and second balloons, pressure sensing,
measurement of one or more upper and lower pressure sensors,
titration of normal saline via an included infusion pump with
titrateable infusion rate, or any combination thereof.
[0118] Some embodiments of the device 100 may have two sets of
pressure sensors (e.g. 504, 505). For example, one set of sensors
may be located at the supra-renal aorta side of the first 102 or
second balloon 103 and the second set of sensors may be located at
the infra-renal aorta side of the first 102 or second balloon 103.
The two sets of sensors may continuously measure pressure and
report pressure data back to the control box 509. The pressure
difference between the two sensors may be displayed by the control
box 509. A physician may then read the pressure difference and
adjust the size of first or second balloon or both using of control
box 509. Alternatively or in combination, the control box 509 may
automatically adjust the size of the first or second balloon or
both in response to measured pressure differences.
[0119] FIG. 6 shows an alternative embodiment of the device 100.
The device 100 may further comprise a side aperture 606 on the
balloon catheter 101 to facilitate application of normal saline or
other medications into the blood. Infusion of the normal saline
into the supra-renal aorta may further augment renal artery blood
flow. Furthermore, infusion of normal saline directly into the
supra-renal aorta may avoid a fluid overload burden on the heart,
which may be of particular importance when patients suffer from
congestive heart failure. Alternatively or in combination, infusion
of normal saline into the supra-renal aorta may help treat CI-AKI
by diluting the concentration of contrast media in the supra-renal
aorta and reducing the potential for adverse effects caused by
contrast media-induced blood hyperviscosity in the kidneys.
[0120] The normal saline or other medications may be infused from
the control box 509 through the catheter 101 into the supra-renal
aorta. In some embodiments, the infusion rate of the normal saline
or medications through the side aperture 606 into aorta may be
controlled by the control box 509. In some embodiments, there may
be a control pump inside the control box 509. In some embodiments,
the control pump may be a separate unit. The medication may a
vasodilatory agent, for example Fenoldopam or the like. The
medication may be infused via the side aperture 606 for prevention
and/or treatment of CI-AKI.
[0121] In some embodiments, the side aperture 606 may be located
between the first balloon 102 and second balloon 103. In some
embodiments the side aperture 606 may be located at the tip of the
catheter 101.
[0122] FIG. 7 shows an embodiment of the device 100 with both the
first balloon 102 and second balloon 103 inflated. Two sensors are
shown as sensors 504 and 505 for example. The first balloon 102 may
be inflated to such an extent that it does not completely occlude
the orifices of the renal arteries. Periodic inflation and
deflation of the first balloon 102, indicated with arrows, may
augment renal artery blood flow.
[0123] FIG. 8 shows an embodiment of the device 100 at the end of a
percutaneous coronary intervention (PCI), for example. Following
PCI, both of the first balloon 102 and the second balloon 103 may
be deflated. The balloons may then be either removed from the
patient or left to remain inside the abdominal aorta, for example
for continuous infusion of normal saline via side aperture 606 for
post-procedural hydration.
[0124] The device 100 may alternatively or in combination comprise
a guidewire 910. FIG. 9 illustrates an exemplary embodiment of
device 100 comprising a guidewire 910. For example, the embodiment
of FIG. 8 may further comprise a guidewire 910 which may be
inserted into the renal artery via the catheter 101. The catheter
may comprise an outer sheath. When the guidewire 910 is inside the
renal artery, the outer sheath catheter 101 may also be inserted
into the renal artery following the path of the guidewire 910.
[0125] In some embodiments the device 100 may further comprise a
guidewire 910 and a unidirectional flow pump 1011. FIG. 10 shows an
embodiment of the device 100 of FIG. 9 further comprising a
unidirectional flow pump 1011. The unidirectional flow pump 1011
may for example be a spinning propeller. The spinning propeller
1011 may be inserted from outer sheath catheter 101 into the renal
artery via the guidewire 910. Activation of the spinning propeller
1011 such that the propeller 1011 spins around the central
guidewire 910 may generate directional augmented renal artery blood
flow toward the kidney.
[0126] FIGS. 11A and 11B show alternative embodiments of the
spinning propeller 1011. The spinning propeller 1011 in some
embodiments is wing shape, fin shape, or the like. The spinning
propeller 1011 may spin around the central guidewire 910 to
generate flow in a unidirectional manner, for example towards a
kidney. In some embodiments, the device 100 may further comprise a
second catheter comprising a second guidewire and a second spinning
propeller for the generation of flow towards a second kidney. In
some embodiments, the second spinning propeller may function
independently of the first spinning propeller to generate augmented
directional blood flow. Alternatively or in combination, the second
spinning propeller may function simultaneously with the first
spinning propeller to augment blood flow towards both of the
kidneys.
[0127] MEMS Pump
[0128] Microelectromechanical systems (MEMS) (also written as
micro-electro-mechanical, MicroElectroMechanical, or
microelectronic and microelectromechanical systems, and the related
micromechatronics) is the technology of very small devices. MEMS
are comprised of components between 1 to 100 micrometers in size
(i.e. 0.001 to 0.1 mm), and MEMS devices generally range in size
from 20 micrometers (20 millionths of a meter) to a millimeter
(i.e. 0.02 to 1.0 mm). They usually comprise a central unit that
processes data (the microprocessor) and several components that
interact with the surroundings such as microsensors. The
fabrication of MEMS evolved from the process technology in
semiconductor device fabrication. The basic techniques include
deposition of material layers and patterning by photolithography
and etching to produce the required shapes. Patterning in MEMS
involves the transfer of a pattern into a material. Typically, a
MEMS pump will have a patterned vibrating chamber connected a flow
inlet and an outlet. Vibration of this chamber is usually driven by
piezoelectricity, such as the product of Bartels
(http://www.micro-components.com). The vibration can also be driven
by pneumatics (see e.g., Chun-Wei Huang, Song-Bin Huang, and
Gwo-Bin Lee, "Pneumatic micropumps with serially connected
actuation chambers," Journal of Micromechanics and
Microengineering, 16(11), 2265, 2006), electrostatics (e.g., Tarik
Bourouina, Alain Bossebuf, and Jean-Paul Granschamp, "Design and
simulation of an electrostatic micropump for drug-delivery
applications," Journal of Micromechanics and Microengineering,
7(3), 186, 1997), or electrothermal mechanism (Rumi Zhang, Graham
A. Jullien, and Colin Dalton, "Study on an alternating current
electrothermal micropump for microneedle-based fluid delivery
systems," Journal of Applied Physics, 114, 024701, 2013).
[0129] Acoustic Wave Pump
[0130] Acoustic streaming can be ideal for microfluidic systems
because it arises from viscous forces, which are the dominant
forces in low Reynolds flows and which usually hamper microfluidic
systems. Streaming force can scale favorably with the size of the
channel, conveying a fluid through which an acoustic wave
propagates and decreases. Because of acoustic attenuation via
viscous losses, a gradient in the Reynolds stresses may be
manifested as a body force that drives acoustic streaming, as well
as streaming from Lagrangian components of the flow. For more
information on the basic theory of acoustic streaming, please see
Engineering_Acoustics/Acoustic streaming. When applied to
microchannels, the principles of acoustic streaming typically
include bulk viscous effects (dominant far from the boundary layer,
though driven by boundary layer streaming), as well as streaming
inside the boundary layer. In a micromachined channel, the
dimensions of the channels are on the order of the boundary layer
thickness, so both the inner and outer boundary layer streaming
needs to be evaluated to have a precise prediction for flow rates
in acoustic streaming micropumps. The derivation that follows
herein is for a circular channel of constant cross-section assuming
that the incident acoustic wave is planar and bound within the
channel filled with a viscous fluid. The acoustic wave may have a
known amplitude and fills the entire cross-section and there are no
reflections of the acoustic wave. The walls of the channel can also
be assumed to be rigid. Importantly, rigid boundary interaction can
result in boundary layer streaming that dominates the flow profile
for channels on the order of or smaller than the boundary layer
associated with viscous flow in a pipe. This derivation can follow
from the streaming equations developed by Nyborg who starts with
the compressible continuity equation for a Newtonian fluid and the
Navier-Stokes and dynamic equations to get an expression for the
net force per unit volume. Eckart may use the method of successive
approximations with the pressure, velocity, and density expressed
as the sum of first and second order terms. Since the first order
terms account for the oscillating portion of the variables, the
time average may be zero. The second order terms arise from
streaming and are time-independent contributions to velocity,
density, and pressure. These non-linear effects due to viscous
attenuation of the acoustic radiation in the fluid can be
responsible for a constant streaming velocity.
[0131] Acoustic wave devices such as surface acoustic wave (SAW)
devices have been in commercial use for more than 60 years, with
their main applications in communications (e.g. filters and
oscillators in mobile phones or televisions). Various microfluidic
acoustic wave pumps have been developed to control, manipulate, and
mix a minute amount of liquid in microliter to picoliter volumes,
including devices based on mechanical moving parts (such as
oscillating membranes), electric fields applied to liquids,
magnetic fields applied to fluids, or by inducing phase changes in
fluids. The surface acoustic wave in some instances is generated by
applying an RF signal to a set of interdigitated transducers (IDTs)
which lie on top of a piezoelectric material. When the frequency,
f, of the RF signal is equal to Vs/p, where Vs is the acoustic
velocity of the substrate/piezoelectric system and p is the
periodic spacing of the IDT electrodes, then constructive
interference occurs and an intense acoustic wave is generated which
travels through the piezoelectric substrate. The mode of the
acoustic wave is determined by the crystallographic orientation of
the piezoelectric material and, in the case of devices using a thin
film piezoelectric, the thickness of the piezoelectric layer. For
microfluidic applications, a component of the acoustic wave is
required in the direction of propagation, and the so-called
Rayleigh mode is commonly employed in which an individual atom
performs elliptical motion in the plane perpendicular to the
surface and parallel to the direction of propagation. However, the
excessive damping of the Rayleigh mode by the liquid means that
this mode is considered to be unsuitable for sensing applications.
The coupling of the acoustic wave into liquid on the surface of the
SAW device, which is required for pumping or mixing, occurs through
the excited longitudinal waves propagating into the liquid at an
angle called the Rayleigh angle, following the Snell law of
diffraction as below: The Rayleigh angle, theta, is defined by
.theta. = sin - 1 ( v L v S ) ##EQU00001##
where V.sub.L is the velocity of the longitudinal wave in the
liquid. However, the energy and the momentum of the longitudinal
wave radiated into the liquid are quite useful for liquid pumping
and mixing (X. Du et al, "ZnO film based surface acoustic wave
micro-pump," Journal of Physics: Conference Series, 76(1), 012047,
2007). A skilled person in the art could prepare and employ an
acoustic wave pump based on the theory provided above.
[0132] In some embodiments, the device 100 may comprise a flow
augmentation means, for example an acoustic wave pump. In some
embodiments, the device 100 may further comprise a guidewire and a
flow augmentation means to generate augmented directional blood
flow into the renal arteries toward the kidney. The flow
augmentation means may, for example, comprise one or more of a
spinning propeller, a micro-electro-mechanical (MEM) micropump, an
acoustic wave pump, or the like. In some embodiments, the flow
augmentation means may be a spinning propeller. In some
embodiments, the flow augmentation means may be a
micro-electro-mechanical (MEM) micropump. In some embodiments, the
flow augmentation means may be an acoustic wave pump.
[0133] The device 100 comprising an acoustic wave pump may be any
of the embodiments described herein. FIG. 12 shows an exemplary
acoustic wave pump employed near the renal arteries. The acoustic
wave pump may include an inflatable first balloon that, when
deflated, may allow blood to flow freely. The first balloon may
then inflate and deflate, as indicated by dashed lines, in a preset
adjustable frequency in order to create an acoustic wave which may
force blood flow to enter the renal arteries, as indicated by the
arrows.
[0134] FIGS. 13A-13B shows the acoustic wave pump of FIG. 12
alternating between an inflated state and a deflated state. The
size of the balloon may be alternated over time with an adjustable
frequency by increasing or decreasing pressure to inflate or
deflate the balloon. The inflation-depletion period (p) may for
example be adjustable. In some embodiments, the shape of the
balloon varies from sphere, cylinder, donut-like to sausage-like
shape.
[0135] In some embodiments, the balloon may be fully inflated such
that its outer circumference contacts the aorta wall, heretofore
defined as 100% inflation. In some embodiments, the balloon may be
inflated to 90%, 80%, 70%, 60%, 50%, 40%, or 30% inflation. The
balloon may alternatively or in combination be inflated within a
range from about 99.9% to about 10%, within a range from about 80%
to about 20%, or within a range from about 70% to about 30%.
[0136] FIGS. 14A-14B illustrates another embodiment of an acoustic
wave pump, wherein two balloons may be involved to create an
acoustic wave. The second balloon may be shaped such that it
surrounds the first balloon. A donut-shaped second balloon may
surround an inflated first balloon. The first balloon may be
inflated to a pre-determined size and may induce a consistent
increased pressure in the abdominal aorta in order to facilitate
blood flow into the renal arteries. The second balloon may be
inflated and delated around the first balloon in order to generate
the acoustic wave. The wave frequency of the donut-like second
balloon may be adjusted to create the desired blood flow toward the
renal arteries. The first balloon and second balloon may each be
fully inflated. Full inflation of the balloons may prevent
unexpected balloon deformation due to aortic blood flow.
[0137] Alternatively or in combination, the device 100 may comprise
a flow disturbing means which may disturb blood flow in the
abdominal aorta so as to reduce the concentration of a contrast
media entering the renal arteries. FIGS. 15A-15B show computer
generated blood flow simulation diagrams. FIG. 15A shows a blood
flow simulation diagram without a flow disturbing means. FIG. 15B
shows a blood flow simulation diagram with a flow disturbing means,
for example a first balloon attached to a tunnel membrane. The
first balloon may for example be a donut-like balloon upon
inflation. The curved lines represent blood flow streamlines. Upon
inflation, the first balloon may form a hollow cylinder. The outer
wall of the inflated first balloon may be in contact with the aorta
wall. When the balloon is inflated, a stagnation region, wherein
the blood flow rate is zero, may be formed adjacent to the upper
wall of the inflated balloon as the blood flow is in laminar
regime. As blood flows through the balloon, a new boundary layer
along the sidewall of the balloon hole may be generated such that
the blood flow is focused towards the very central part of the
abdominal aorta. Focusing blood flow towards the center of the
aorta from the periphery of the aorta may result in a retardation
of the flow of a contrast media from the supra-renal aorta into the
orifice of the renal artery. By reducing the flow of contrast media
toward the kidneys, CI-AKI may be prevented.
[0138] The streamlines, represented by the curved lines in FIGS.
15A-15B, indicate the blood flow routes from the supra-renal aorta.
As shown in FIG. 15A, the blood flow streamlines travel from the
supra-renal aorta directly into the renal arteries, such that an
injected contrast media may enter the renal arteries at a high
concentration. In FIG. 15B, the blood flow streamlines curve toward
the central part of the aorta before passing through the first
balloon. The blood flow streamlines travel from the supra-renal
aorta, are diverted past the renal arteries towards the infra-renal
aorta, before flowing back towards the renal arteries. An injected
contrast media may therefore be diluted in the intra-renal aorta
prior to reaching the renal arteries at a lower concentration.
[0139] The results of the blood flow simulation shown in FIGS.
15A-15B may provide guidance for the design of embodiments of a
flow disturbing means. In some embodiments, the flow disturbing
means may be a tunnel membrane adapted to fit inside an aorta wall.
The tunnel membrane may be attached to the first balloon. In some
embodiments, the flow disturbing means may be an umbrella-like
component attached to either the catheter or the first balloon. The
umbrella-like component may reduce blood flow by being positioned
either above the renal arteries, i.e. in the supra-renal aorta, or
below the renal arteries, i.e. in the infra-renal aorta. The flow
disturbing means may, for example, be an umbrella-like blood flow
reducing component attached to the catheter and positioned at
supra-renal aorta. A person skilled in the art will readily
recognize any similar shapes, structures, or functions to an
umbrella-like blood flow reducing component.
[0140] The flow disturbing means may be any device that can disturb
blood flow and result in lower renal artery blood intake directly
from the supra-renal aorta. The flow disturbing means may be
applied to any of the device embodiments described herein, for
example the embodiments of FIGS. 16A-16D, 17A-17C, or the like.
[0141] One or more of the first balloon and the disturbing means
may be coated with contrast-media absorber so as to remove contrast
media from the blood, further diluting the concentration of the
contrast media and reducing potential harm to the kidneys, for
example CI-AKI, caused by the contrast media.
[0142] FIG. 16A illustrates another embodiment of a device 100 for
treating or preventing AKI, for example CI-AKI. As illustrated in
FIG. 16A, the device 100 may comprise a catheter 101 with a first
balloon 102 attached to a disturbing means. The disturbing means
may for example comprise a tunnel membrane 1603A as shown. FIG. 16B
shows a top-down cross-sectional view of the embodiment of FIG. 16A
wherein at least one connection tube 304 from the catheter 101 is
depicted. The first balloon may for example be donut-shaped such
that a hollow area is created between the inner edge of the
inflated balloon 102 and the catheter 101 through which blood may
flow from the supra-renal aorta to the infra-renal aorta.
[0143] The device 100 may further comprise a second balloon 103 as
shown in FIG. 16D. The second balloon 103 may be attached to the
tunnel membrane 1603A. The first balloon 102 may for example be
located in the supra-renal aorta and be larger in diameter than the
second balloon 103 such that the first balloon 102 may contact the
aorta wall. The second balloon 103 may provide drag to deploy the
tunnel membrane 1603A. In some embodiments the first balloon 102
may not fully inflate to contact the aorta wall and therefore leave
a small space around the first balloon 102 through which blood may
pass.
[0144] The disturbing means may alternatively or in combination
comprise an umbrella-like blood flow reducing component 1603B as
shown in FIG. 16C. During insertion of the device 100, the
umbrella-like component 1603B may be folded to allow free flow of
blood. Upon being positioned such that the disturbing means sits
near or below the renal arteries, the umbrella-like component 1603B
may be unfolded by the downward direction of blood flow.
[0145] The disturbing means may for example be made of soft
plastics. In some embodiments, the disturbing means may for example
be made of semi-soft plastics. Alternatively or in combination, the
disturbing means may for example be made of metal having
flexibility, such as a metal wire. In some embodiments the tunnel
membrane may be a flexible film such as one or more of
polytetrafluoroethene (PTFE), expanded polytetrafluoroethene
(ePTFE), silicone rubber, polyurethane, poly(ethylene
terephthalate), polyethylene, polyether ether ketone (PEEK),
polyether block amide (PEBA), or the like, or any combination
thereof.
[0146] In some embodiments, the infra-renal side of the balloon or
of the disturbing means, for example, a tunnel membrane, may inject
normal saline or other medications into the aorta via one or more
injection hole. Injection of normal saline may, for example, dilute
a contrast media before flowing into the renal arteries. The
injection hole or multiple injection holes may be located on the
first balloon. At least one injection hole or multiples injection
holes may be located on the catheter near the first balloon. At
least one injection hole or multiple injection holes may be part of
one or both of the first balloon and the catheter. In some
embodiments, the injection holes may be located at an infusion
tube. The infusion tube may for example be made of one or more of a
material selected from the group consisting of teflon,
polyoxymethylene copolymer, polyimides, polycarbonate,
polyetherimide, polyetheretherketone, polyethylene, polylactic
acid, polylactide acid, polystyrene, polyurethane, PVC,
thermoplastic elastomer, and combinations thereof, and the
like.
[0147] FIGS. 17A-17C show another embodiment of a flow disturbing
means. As illustrated in FIG. 17A, the flow disturbing means may be
a cone-shaped wire device 1702 partially covered with tunnel
membrane 1703 which is deployed from catheter 101. Tunnel membrane
1703 may be substantially similar to the tunnel membrane 1603A of
FIG. 16. The cone-shaped wire device 1702 may comprise a plurality
of wires 1710.
[0148] FIG. 17B shows the device 1702 located in the abdominal
aorta with exemplary specifications. The diameter of the distal
opening 1704 may for example be about 3 to about 3.2 cm, or
preferably about 3.0 cm. The cone-shaped wire device 1702 may have
outer wire rim 1704 dimensions such that the device 1702 may fit
either tightly within the aorta, for example, a diameter of about 3
to about 3.2 cm, or loosely situated with little space between the
device 1702 and the aorta wall allowing blood seeping through, for
example a diameter of less than about 3 cm. The diameter of the
distal opening 1704 may be designed based on various diameters of a
patient's aorta in which the device 1702 will be deployed, which
typically range from about 5 cm to about 2 cm. The distal opening
1704 may for example have a diameter of about 5 cm to about 1.5 cm;
or a diameter of about 4.5 cm to about 1.7 cm. In some embodiments,
the distal opening 1704 may have a diameter of about 4 cm to about
1.8 cm, for example about 3.5 cm to about 1.8 cm or about 3 cm to
about 2.0 cm.
[0149] The height 1706 of the tunnel membrane 1703 may be about 1.5
cm to about 4 cm, for example, about 2 cm to about 3.5 cm or about
2.5 cm to about 3.0 cm. In some embodiments, the height 1706 of the
tunnel membrane 1703 may be about 2 cm, about 3 cm, or about 4
cm.
[0150] The tunnel membrane 1703 may extend from the edge of the
distal opening 1704 to the proximal opening 1705 of the cone-shaped
wire device 1702. The proximal opening 1705 may allow blood to flow
through the tunnel membrane 1703 with restricted speed such that
blood flow is disturbed to allow the renal arteries to intake blood
from the infra-renal aorta. Disturbing blood flow may dilute an
injected contrast media prior to entering the renal arteries. In
some embodiments, effective blood flow disturbance may be generated
with the diameter of the proximal opening 1705 at about one-fourth
to about three-fourths of the diameter of the distal opening 1704.
In some embodiments, the diameter of the proximal opening 1705 may
be about one-third of the diameter of the distal opening 1704. For
example, the diameter of the bottom opening 1705 may be about 1.0
cm when the diameter of the distal opening 1704 is about 3 cm. The
blood releasing height 1709 from the proximal opening 1705 may be
designed to be about one-half to about three times the diameter of
the proximal opening 1705. The ratio relationship between the blood
releasing height 1709 and proximal opening 1705 may be based on how
the wire device 1702 restricts blood flow to create disturbance,
the structural strength of the wire device 1702, and the diameter
relationship between the distal opening 1704 and the proximal
opening 1705.
[0151] To support the structure of an embodiment such as the
cone-shaped wire device 1702, the wire device may comprise at least
3 wires 1710. In some embodiments, there may be 4 to 24 wires, 5 to
22 wires, 6 to 20 wires, 8 to 18 wires, or 10 to 16 wires 1710. In
some embodiments, there may be 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 15, 16, 17, 18, 19, or 20 wires 1710 in the wire device 1702
partially covered by the tunnel membrane 1703. A skilled person in
the art may prepare a wire device in accordance with the practice
of the present disclosure to any number of wires suitable to
provide a disturbing means. The wire may be made of any
superelastic or pseudoelastic material, for example nitinol, alloys
of copper-zinc-aluminum (CuZnAl), alloys of copper-aluminum-nickel
(CuAlNi), alloys of copper-aluminum, alloys of nickel-titanium, or
any combination thereof. In some embodiments, the superelastic
material may comprise one or more of copper, aluminum, nickel,
titanium, or any combination thereof. Specific structures may be
formed by routing the wires, for example by bending or weaving the
wires into a final shape. Alternatively or in combination, specific
structures may be formed by cutting a superelastic tube, for
example laser cutting out portions to leave a final wire structure.
Alternatively or in combination, specific structures may be for my
cutting a superelastic fleet, for example laser cutting out parts
and annealing the fleet into a final cone-shape.
[0152] Pseudoelasticity, sometimes called superelasticity, is an
elastic (reversible) response to an applied stress, caused by a
phase transformation between the austenitic and martensitic phases
of a crystal. It is exhibited in shape-memory alloys.
Pseudoelasticity is from the reversible motion of domain boundaries
during the phase transformation, rather than just bond stretching
or the introduction of defects in the crystal lattice (thus it is
not true superelasticity but rather pseudoelasticity). Even if the
domain boundaries do become pinned, they may be reversed through
heating. Thus, a superelastic material may return to its previous
shape (hence, shape memory) after the removal of even relatively
high applied strains.
[0153] The shape memory effect was first observed in AuCd in 1951
and since then it has been observed in numerous other alloy
systems. However, only the NiTi alloys and some copper-based alloys
have so far been used commercially.
[0154] The disturbing means of device 100, for example the
cone-shaped wire device 1702, may further comprise an infusion tube
1707 and one or more injection hole 1708 for delivery of normal
saline or other medications. Delivery of normal saline, for
example, may further dilute the contrast media prior to flowing
into the renal arteries. As shown in FIG. 17C, one or more
injection holes 1708 may be located at the distal opening 1704 or
the proximal opening 1705, or a combination thereof. For example, a
plurality of injection holes 1708 may be located at both of the
distal 1704 and proximal 1705 openings of the cone-shaped wire
device 1702. Alternatively or in combination, the one or more
injection hole 1708 may be located on the catheter 101, for example
near the tip of the catheter 101 where the disturbing means is
deployed.
[0155] In some embodiments, the cone-shaped wire device 1702 may
comprise an upper cylinder portion 1811 as illustrated in FIG. 18A.
The cone-shaped wire device 1702 may be partially covered with
tunnel membrane 1703 from the rim of the distal opening 1704 to the
proximal opening 1703. The device 1702 may be deployed from the
catheter 101. FIG. 18B shows a top-down view of the device 1702
with upper cylinder portion 1811. FIG. 18C shows a bottom-up view
of the device 1702 with upper cylinder portion 1811. FIG. 18D
provides an isometric view of the device 1702 with upper cylinder
portion 1811.
[0156] The upper cylinder portion 1811 may be used to form tight
contact of the device with the aorta wall. Tight contact may
support the device 1702 against high pressure due to a high blood
flow rate. Tight contact between the device 1702 and the aorta wall
may further prevent a contrast media from leaking through the
contact interface.
[0157] To avoid occlusion of the renal arteries branching from the
supra-renal aorta by upper cylinder portion 1811, which is about
0.5 cm apart, the height of the upper cylinder portion 1811 should
not be more than 0.5 cm, or about the distance between the renal
arteries and the supra-renal aorta. The height 1806 of the tunnel
membrane 1703 from the distal opening 1705 to the proximal opening
1704 should be about 1.5 cm to about 4 cm, for example about 2 cm
to about 3.5 cm or about 2.5 cm to about 3.0 cm.
[0158] FIG. 19 shows an embodiment of a cone-shaped wire device
1702 being deployed inside the abdominal aorta. FIG. 19A shows the
device 1702 with the tunnel membrane 1703 at the beginning of
deployment from the catheter 101. FIG. 19B shows the tunnel
membrane 1704 partially deployed into the abdominal aorta. FIG. 19C
shows the tunnel membrane 1704 fully deployed into the abdominal
aorta.
[0159] The catheter device 100 comprising a cone-shaped wire device
1702 may further comprise at least one position indication means
105, for example a radio-opaque marker or the like, to determine
the location of the catheter 101 for proper deployment of the
tunnel membrane 1703 in the supra-renal aorta near the orifices of
the bilateral renal arteries. The device 1702 may for example be
inserted into the abdominal aorta via either a transfemoral
arterial approach, a trans-brachial artery approach, or a
trans-radial artery approach.
[0160] In some embodiments, the cone-shaped wire device 1702 may
further comprise a blood flow diversion means in conjunction with
the tunnel membrane, wherein deployment of the flow diversion means
inside the abdominal aorta may occlude the orifices of both sides
of the renal arteries while continuing to allow blood to flow
through the tunnel membrane. FIG. 20A shows an exemplary embodiment
of a device 100 comprising a cone-shaped wire device 1702
comprising a catheter 101, tunnel membrane 1703, infusion tube
1707, multiple supporting wires 1710, and a radio-opaque marker 105
on the tip of the catheter 101. The device 1702 may further
comprise one or more of a blood flow diversion means 203, for
example a seal membrane, and a donut-like balloon 204. FIG. 20B
shows the embodiment of FIG. 20A with donut-like balloon 204 in a
deflated state. The donut-like balloon 204 may be positioned
between the tunnel membrane 1703 and the seal membrane 203. FIG.
20C shows the donut-like balloon 204 in an inflated state.
Inflation of the donut-like balloon 204 deploys the seal membrane
203. The donut-like balloon 204 may further comprise at least one
aperture 207 to allow for infusion of normal saline or medications
into the abdominal aorta. The at least one aperture 207 may be
substantially similar to the side aperture 606 previously described
herein. FIG. 20D shows the upper rim of the tunnel membrane 1703
positioned in the supra-renal aorta 208 near the orifices of the
right renal artery 210 and the left renal artery 211. Deployment of
the seal membrane 203 via inflation of the donut-like balloon 204
may further reduce blood flow from the infra-renal aorta 209 to the
renal arteries 210, 211. When a bolus influx of contrast media or
other harmful agent occurs, deployment of the device 100 may
prevent blood flowing from the supra-renal aorta from entering the
renal arteries where the contrast media may have toxic effects.
[0161] FIGS. 21A-21C illustrates yet another embodiment of a
cone-shaped device 1702. The device 100 comprises catheter 101
which may allow the deployment of tunnel membrane 1703, a
donut-like balloon 203, multiple supporting wires 1710, and a
radio-opaque marker 105 on the tip of the catheter 101. At least
one aperture 207 may be on the donut-like balloon 203, for example
to allow infusion of normal saline or medication. FIG. 21A shows
the donut-like balloon 203 in a deflated state. The donut-like
balloon 203 is positioned at the lower end of the tunnel membrane
1703. FIG. 21B shows the donut-like balloon 203 in an inflated
state. The size of the donut-like balloon 203 may vary in order to
optimally exert its function. FIG. 21C shows the upper rim of
tunnel membrane 1703 positioned in the supra-renal aorta 208 near
the orifices of the bilateral renal arteries 210, 211 with the
donut-like balloon 203 inflated to further reduce blood flow from
infra-renal aorta 209 to the right renal artery 210 and the left
renal artery 211 such that a bolus influx of contrast media or
other harmful agent flowing from the supra-renal aorta 208 may be
prevented from entering the renal arteries 210, 211 and having
toxic effects.
[0162] FIGS. 22A-22B illustrate yet another embodiment of device
100 deployed in the abdominal aorta. FIG. 22A shows an embodiment
of the device 100, for example the embodiment of FIG. 17 which
comprises a cone-shaped wire device 1702 deployed from catheter
101. The cone-shaped wire device 1702 may comprise a tunnel
membrane 1703, infusion tube 1707, and one or more supporting wires
1710. The device 1702 may further comprise a position indication
means 105, such as a radio-opaque marker. The radio-opaque marker
105 may be on the tip of catheter 101. At least one aperture 207
may be on the infusion tube 1707 to allow infusion of normal saline
or medication into the abdominal aorta. The aperture 207 may be
substantially similar to the injection hole 1708 previously
described herein. FIG. 22B shows the device positioned in the
supra-renal aorta near the orifices of the bilateral renal arteries
such that the upper rim of the tunnel membrane 1703 makes contact
with the inner wall of the aorta and diverts blood flow away from
the renal arteries. Saline infusion through aperture 207, as
indicated by arrows, may dilute a contrast agent prior to entering
the renal arteries.
[0163] FIG. 23 shows yet another embodiment of catheter device 100
comprising a balloon catheter with a blood flow disturbing means.
The device 100 may comprise a catheter 101, tunnel membrane 1703,
first balloon 102 at the distal end of the tunnel membrane, second
balloon 103 at the proximal end of the tunnel membrane, at least
one infusion tube 1707 for infusing fluid into or out of the
balloons, at least one position indication means 105, and at least
one aperture 106 on the tunnel membrane with a wire 107 surrounding
the aperture such that opening of the aperture is controlled by the
wire. The tunnel membrane 1703 may be a flow disturbing means, for
example device 1702 as previously described herein, such that the
tunnel membrane 1703 shunts blood flowing from the supra-renal
aorta through the tunnel membrane 1703, bypassing the renal
arteries, into the intra-renal aorta. Flow disturbance may be
further facilitated by inflation of one or both of the distal
balloon 102 and proximal balloon 103 to contact the wall of the
supra-renal aorta and the wall of the infra-renal aorta,
respectively. The aperture 106 may be substantially the same as the
aperture 207 described previously herein. The wire 107 surrounding
the aperture 106 may be used to keep the aperture 106 closed during
the shunting period. The shunting period may be synchronized with
the injection of a contrast media by a physician. The shunting
period should be kept to a minimum amount of time to shunt the
contrast media but not long enough to cause renal ischemia by
preventing blood flow to the kidneys. The kidneys are resistant to
transient ischemia, therefore the shunting period may be tuned to
avoid ischemia.
[0164] The position indication means 105 may for example be a
radio-opaque marker. One or more position indication means 105 may
be located on the tip of the catheter 101, on the proximal balloon
103, on the distal balloon 102, or any combination thereof. The
position indication means 105 may be used to monitor the position
of the device 100 upon insertion, during use, and during removal.
The device 100 may be inserted into the abdominal aorta for example
by using either a trans-femoral arterial approach, a trans-brachial
artery approach, or a trans-radial artery approach.
[0165] In some embodiments, the aperture 106 and the surrounding
wire 107 comprise at least one set of the aperture 106 and the
surrounding wire 107 on the tunnel membrane. In some embodiments,
there are one to four sets, two to six sets, three to nine sets,
four to twelve sets, five to fifteen sets, or six to eighteen sets.
In some embodiments, there may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13, 14, 15, 16, 17, or 18 sets of the aperture and the
surrounding wire on the tunnel membrane. If needed, a person
skilled in the art can prepare a wire device in accordance with the
practice of the present disclosure to any number sets of the
aperture and the surrounding wire suitable to provide a flow
passage means. The wire may be any superelastic material, for
example nitinol. The wire may be made of any superelastic or
pseudoelastic material, for example nitinol, alloys of
copper-zinc-aluminum (CuZnAl), alloys of copper-aluminum-nickel
(CuAlNi), alloys of copper-aluminum, alloys of nickel-titanium, or
any combination thereof. In some embodiments, the superelastic
material may comprise one or more of copper, aluminum, nickel,
titanium, or any combination thereof.
[0166] Embodiments of device 100 described herein may be used in
combination with a means to synchronize injection of contrast agent
and/or medication for the treatment or prevention of AKI. FIGS.
24A-24B show an embodiment of an injection device which may be used
as a synchronization means. FIG. 24A shows the injection device
comprising an injector 500, contrast agent chamber 501 with
contrast agent outlet 503, medication chamber 502 with medication
outlet 504, and a common injection actuator 505. The medication
chamber 502 may for example contain normal saline. The chambers 501
and 502 comprising outlets 503 and 504 respectively may for example
be syringes. Injection may for example occur by depressing the
injector 500 in the direction of outlets 503 and 504. The
proportion of contrast agent and normal saline injected can be
adjusted by adjusting the relative diameters or the relative
dimensions of syringes 501 and 502 to control the flow rate. The
injection outlet 504 of normal saline may further be connected to a
volume reservoir 506 for generating a time difference between the
actual arrival time of the contrast agent and the actual arrival
time of the inside the abdominal aorta, as illustrated in FIG.
24B.
[0167] Embodiments of the device 100 described herein may be used
alternatively or in combination with a means to balance fluids
entering and leaving the body of a patient. FIG. 25 shows an
embodiment of a balancing means 600 comprising a fluid-containing
box 601, an inlet conduit 602 to provide fluid flow into the body,
and an outlet conduit 603 to provide for fluid to flow out of the
body. The box 601 may contain two chambers within a single larger
container in order to preserve a total volume of the inflow and
outflow fluids. A pump 604 may be used to actively pump fluids.
Fine measuring units 605 may be used to measure the volumes of the
inflow and outflow fluids.
[0168] Another aspect of the present disclosure provides a method
for treating CI-AKI. The method may comprises steps of: inserting
the catheter device into the abdominal aorta; placing the catheter
in the supra-renal aorta; and deploying the disturbing means at a
position which allows for blood flow disturbance to dilute the
contrast media before being taken into the renal arteries.
Insertion of the device into the abdominal aorta may for example
occur by either a trans-femoral artery approach a trans-branchial
artery approach, or a trans-radial artery approach. In some
embodiments, the catheter device may further include a guidewire
and a flow augmentation means. In some embodiments, the method may
further comprise infusion of one or more of normal saline or
medications into the supra-renal abdominal aorta by one or more
injection holes in fluid communication with an infusion tube, the
catheter, or both.
[0169] Another aspect of the present disclosure may provide a
method for treating CI-AKI is disclosed. The method may comprise
steps of: inserting the catheter device comprising a balloon
catheter having a first balloon, a second balloon, at least one
sensor into abdominal aorta; placing the balloon catheter at a
position such that the first balloon is located in the supra-renal
aorta near the orifices of the bilateral renal arteries and the
second balloon is located in the infra-renal aorta near the
orifices of the bilateral renal arteries; inflating the first
balloon to occlude the orifices of both sides of the renal arteries
during the application of contrast media; deflating the first
balloon after the contrast media has been completely employed;
inflating the second balloon to an extent so as not to fully
occlude blood flow in the aorta; deflating the second balloon; and
optionally infusing normal saline and/or suitable medication into
the supra-renal aorta via a side aperture.
[0170] In some embodiments, insertion of the catheter device into
the abdominal aorta may for example occur by either a trans-femoral
arterial approach, a trans-brachial artery approach, or a
trans-radial artery approach. In some embodiments, the balloon
catheter may further comprise a guidewire and a spinning propeller.
In some embodiments, the method further comprises inserting a
guidewire into the renal artery. In some embodiments, the method
further comprises inserting a spinning propeller into renal artery
along the guidewire. In some embodiments, the method further
comprises spinning the spinning propeller around the central
guidewire to generate directional augmented renal artery blood flow
toward the kidney.
[0171] The present disclosure may also provide a system comprising
a catheter device, such as described herein, for treating AKI. In
some embodiments, the AKI is CI-AKI. In some embodiments, the
device may comprise a catheter, a position indication means on the
catheter, and a flow disturbing means retractable into the
catheter, wherein the flow disturbing means may be positioned in
the suprarenal aorta to provide blood flow disturbance as described
herein. In some embodiments, the device may comprise a balloon
catheter having a first balloon, a second balloon and at least one
sensor associated with the second balloon. In some embodiments, the
device comprises two sensors as described herein. In certain
embodiments, the balloon catheter may further comprise a side
aperture for infusing normal saline or medication.
[0172] FIGS. 26A-26G show yet another embodiment of the present
disclosure. The catheter device 100 may comprise a catheter shaft
2600 actuated to deploy an occlusive element 2601 to occlude the
renal artery openings. The occlusive element 2601 may, for example,
be an expandable mesh braid. The expandable mesh braid may comprise
a tubular, metal mesh braid comprising a plurality of mesh
filaments. The expandable mesh braid may comprise a shape-memory
material such as Nitinol and may be biased to be in the expanded
configuration. The device may further comprise a position
indication features, for example, at least a portion of the
catheter device may be radio-opaque.
[0173] FIG. 26A shows a catheter shaft 2600 comprising an outer
shaft 2602 and an inner shaft 2603 disposed therein which are
translatable relative to one another. The distal end 2604 of the
expandable mesh braid 2601 may be coupled to the inner shaft 2603
while the proximal end 2605 of the expandable mesh braid 2601 may
be coupled to the outer shaft 2602 such that translation of the
inner shaft 2603 relative to the outer shaft 2602 deploys or
collapses the expandable mesh braid 2601. The catheter shaft 2600
may further comprise a cover 2606 to protect the catheter shaft
device 100 during insertion into the abdominal aorta. The cover
2606 may be removed upon positioning the catheter shaft device 2600
at a desired location.
[0174] FIG. 26B shows the catheter shaft device 100 with expandable
mesh braid 2601 coupled to the inner 2603 and outer 2602 shafts.
The expandable mesh braid 2601 is shown in a low-profile
configuration which may be used for delivery of the device 100
through the vasculature prior to deployment. The low-profile
configuration may be axially elongated and radially collapsed.
[0175] FIG. 26C shows the catheter shaft device 100 following
actuation of the inner shaft 2603 relative to the outer shaft 2602
for deployment of the expandable mesh braid 2601. The expandable
mesh braid 2601 is shown in an expanded configuration such that the
device 100 occludes the renal artery ostia (also referred to herein
as orifices) to prevent contrast agent from flowing into the renal
arteries of a patient when a bolus of the contrast agent has been
introduced into the vasculature. The expanded configuration may be
axially foreshortened and radially expanded. In the expanded
configuration, the expandable mesh braid 2601 may comprise a
minimally porous portion 2607, for example a high-density mesh
brain filament portion. The minimally porous portion 2607 may be a
region where the braid 2601 is axially foreshortened to increase
filament density. The expandable mesh braid 2601 in the expanded
configuration may comprise one or more porous end portions 2608
adjacent to the minimally porous portion 2607 so as to allow blood
to flow through the braid 2601 from the supra-renal aorta to the
infra-renal aorta, bypassing the occluded renal arteries. The one
or more porous end portions 2607 may comprise low mesh braid
filament density portions.
[0176] Actuation of the catheter shaft for deployment of the
expandable mesh braid may, for example, comprise translating the
inner and outer shafts such that the distal end of the outer shaft
moves closer to the distal end of the inner shaft.
[0177] FIG. 26D shows a prototype of a catheter shaft device 2600
with expandable mesh braid 2601. The embodiment comprises a tubular
metal mesh braid 2601 comprising a plurality of mesh filaments made
of Nitinol, an outer shaft 2602, and an inner shaft 2603. The
distal end 2604 of the expandable mesh braid 2601 is coupled to the
inner shaft 2603 while the proximal end 2605 of the expandable mesh
braid 2601 is coupled to the outer shaft 2602. Translation of the
inner shaft 2603 relative to the outer shaft 2602 deploys or
collapses the expandable mesh braid. In its expanded configuration,
the expandable mesh braid 2601 comprises a minimally porous portion
2607 with which to occlude the orifices of the renal arteries. The
expandable mesh braid further comprises two porous end portions
2608 which may allow blood to flow through the braid 2601 from the
supra-renal aorta to the infra-renal aorta, bypassing the occluded
renal arteries. FIG. 26E shows the expandable mesh braid 2601 with
fully open mesh. FIG. 26F shows the expandable mesh braid 2601 with
a partially collapsed mesh. FIG. 26G shows the expandable mesh
braid 2601 with fully collapsed mesh.
[0178] The catheter shaft device 100 may further comprise a
time-delayed release mechanism configured to automatically collapse
the expandable mesh braid after a pre-determined amount of time
following deployment. The time-delayed release mechanism may, for
example, comprise an energy accumulation and storage component and
a time-delay component. For example, the time-delayed release
mechanism may comprise a spring with a frictional damper, an
example of which is described in FIG. 31. The energy accumulation
and storage component may for example be a spring or spring-coil or
the like. The time-delayed release mechanism may for example be
adjustable by one or more of the user, the manufacturer, or both.
The time-delayed release mechanism may further comprise a
synchronization component to synchronize the injection of a
contrast media or other harmful agent with the opening or closing
of the catheter shaft device. For example, injection may be
synchronized with occlusion of the renal arteries by the expandable
mesh braid such that a contrast media may be prevented from
entering the renal arteries.
[0179] FIGS. 27A-27D show the deployment of the embodiment of FIGS.
26A-26G. Similar deployment steps may be used for all of the
embodiments described herein. As shown in FIG. 27A, the device 100
may be inserted into the abdominal aorta via the femoral artery.
Alternatively, the device 100 may be inserted into the abdominal
aorta via the branchial or radial arteries. As shown in FIG. 27B,
the device 100 may be guided to a desired location within the
abdominal aorta by monitoring a position indication means, for
example a radio-opaque marker or a radio-opaque portion of the
catheter. The device 100 may for example be positioned such that
deployment of the expandable mesh braid 2601 occludes the orifices
of the renal arteries. FIG. 27C shows the expandable mesh braid
2601 deployed at a desired position so as to occlude the orifices
of the renal arteries. The expandable mesh braid 2601 may be
deployed prior to or simultaneously with injection of a contrast
agent into the abdominal aorta of a patient so as to prevent the
contrast agent from entering the renal arteries. After the bolus of
contrast agent has been introduced, the expandable mesh braid 2601
may be collapsed to allow blood flow to the renal arteries to
resume, as shown in FIG. 27D.
[0180] The expandable mesh braid may for example be made of a
superelastic material such as nitinol. The braid may be made of any
superelastic or pseudoelastic material, for example nitinol, alloys
of copper-zinc-aluminum (CuZnAl), alloys of copper-aluminum-nickel
(CuAlNi), alloys of copper-aluminum, alloys of nickel-titanium, or
any combination thereof. In some embodiments, the superelastic
material may comprise one or more of copper, aluminum, nickel,
titanium, or any combination thereof. The expandable mesh braid may
for example be made of steel or any other mesh-grade material. The
expandable mesh braid may be coated with a hydrophobic coating, a
hydrophilic coating, or a tacky coating for enhanced flow
diversion. The shape of the braid may be adjusted to better fit
into the geometry of the abdominal aorta, for example the diameter
of the lower part of the braid may be smaller than the diameter of
the upper part of the braid.
[0181] FIGS. 28A-28C show another embodiment of the present
disclosure. The catheter device 2800 may comprise a catheter 101
with a first balloon 102 and a second balloon 103 disposed on a
proximal portion thereof. The first balloon 102 may be disposed on
a first lateral side of the proximal portion of the catheter 101.
The second balloon 103 may be disposed on a second lateral side of
the proximal portion of the catheter 101, for example opposite the
first balloon 102.
[0182] FIG. 28A shows a prototype of a balloon catheter device 2800
having two ellipsoidal balloons 102 and 103 in a collapsed
configuration. FIG. 28B shows the device 2800 in an expanded
configuration. The first and second balloons 102, 103 may for
example be ellipsoidal as shown. The balloons 102, 103 may form a
dumb-bell or butterfly-like shape about the catheter 101 in
cross-section when expanded from the collapsed configuration (FIG.
28A) to the expanded configuration (FIG. 28B). The balloons 102,
103 may be shaped so as to occlude the left and right renal
arteries when expanded while allowing blood to flow between the
balloons 102, 103 along the catheter shaft 101. In some instances,
the balloons 102, 103 may be a single balloon disposed about the
catheter 101 with a first balloon portion and a second balloon
portion shaped similarly to the first and second balloons 102, 103
described herein. As discussed further below, a position indication
feature 2900 may be disposed on the surfaces of the balloons 102,
103 to facilitate the determination of the position of the balloons
102, 103 and of whether the renal artery ostia are occluded. As
shown in FIGS. 28A and 28B, the position indication feature 2900
may comprise a plurality of longitudinal radio-opaque markers and a
radio-opaque marker 2900a disposed on the catheter 101 between the
balloons 102, 103.
[0183] FIG. 28C shows the device 2800 in the expanded configuration
inside a model abdominal aorta 2850. The catheter balloon device
2800 is shown positioned within a model abdominal aorta 2850.
Generally, the one or more balloons 102, 103 may be positioned
adjacent the orifices of the right renal artery 210 and the left
renal artery 211, for example spanning between the supra-renal
aorta 208 and the infra-renal aorta 209, thereby controlling blood
flow to any of the right renal artery 210, left renal artery 211
and/or infra-renal aorta 209. While occluding the renal arteries
102, 103, the balloons 102, 103 may not completely occlude the
aorta 2850 and may allow blood flow through the gaps between the
balloons 102, 103 and the catheter 101. In cross-section, the
expanded balloons 102, 103 may assume a dumbbell or butterfly
shape, for example, as described herein.
[0184] Generally, the balloons 102, 103 may be of any size and/or
shape. In particular the size and/or shape may be selected to
control the amount of occlusion for each of the left and right
arteries. For example, the renal arteries may be located at
different distances down the length of the aorta (e.g., viewing the
aorta along the coronal plane, the left and right renal arteries
may branch away from the aorta at different distances from the
aortic arch). In such instances, it may be beneficial to employ
balloons that are ellipsoidal (e.g., greater in length along a
longitudinal direction of the aorta than in diameter), thereby
capable of occluding both the left and right renal artery upon
being placed in the initial position. In some instances, the renal
arteries may branch at different angles (as viewed along the axial
plane) from the aorta between subjects or groups of subjects. In
such instances, it may be beneficial to employ balloons which are
positioned to match the branching architecture of the patient or
group of patients (e.g. balloons which are positioned opposite one
another on the catheter for patients with branching opposite one
another or balloons which are position less than 180.degree. apart
about the catheter for patients with branching less than
180.degree. apart). In some instances, it may be beneficial to
employ balloons shaped to deform when contacting the aorta and
"spread" along the wall in order to occlude a typical range of
angles for a particular group of subjects. In some instances it may
be beneficial to employ balloons sized or shaped to occlude a
typical range of angles for a particular group of subjects. The
typical range of angles may vary from subject group (e.g. patient
population) to subject group and the spread, angle, size, and/or
shape of the balloons may be configured to perform for a particular
subject group based on the typical range of branching angles. In
some embodiments, the size and/or shape of the balloon may be
specific for a particular group of subjects. For example, younger
subjects (e.g., under 15 years of age) may require balloons that
are shorter in length and/or width (e.g., in an un-inflated state)
as compared to adults (e.g., 15 years of age and older). In another
example, balloons of a particular size and/or shape may be suitable
for subjects originating from a given geographical location or
ethnic background due to genetic and physiological variations
between subjects or groups of subjects (e.g., Asians vs.
Caucasians). Non-limiting examples of balloon length include about
1 millimeter (mm), about 2 mm, about 3 mm, about 4 mm, about 5 mm,
about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about
11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16
mm, about 17 mm, about 18 mm, about 19 mm, about 20 mm, about 21
mm, about 22 mm, about 23 mm, about 24 mm, about 25 mm, about 26
mm, about 27 mm, about 28 mm, about 29 mm, about 30 mm, about 31
mm, about 32 mm, about 33 mm, about 34 mm, about 35 mm, about 36
mm, about 37 mm, about 38 mm, about 39 mm, about 40 mm, 41 mm,
about 42 mm, about 43 mm, about 44 mm, about 45 mm, about 46 mm,
about 47 mm, about 48 mm, about 49 mm, about 50 mm, about 60 mm,
about 70 mm, about 80 mm, about 90 mm, about 100 mm, or greater
than about 100 mm. Non-limiting examples of balloon diameter
include about lmillimeter (mm), about 2 mm, about 3 mm, about 4 mm,
about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about
10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15
mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, about 20
mm, about 21 mm, about 22 mm, about 23 mm, about 24 mm, about 25
mm, about 26 mm, about 27 mm, about 28 mm, about 29 mm, about 30
mm, about 31 mm, about 32 mm, about 33 mm, about 34 mm, about 35
mm, about 36 mm, about 37 mm, about 38 mm, about 39 mm, about 40
mm, 41 mm, about 42 mm, about 43 mm, about 44 mm, about 45 mm,
about 46 mm, about 47 mm, about 48 mm, about 49 mm, about 50 mm,
about 60 mm, about 70 mm, about 80 mm, about 90 mm, about 100 mm,
or greater than about 100 mm. In some embodiments, the diameter of
the balloon may change from a proximal end of the balloon to a
distal end of the balloon. For example, the balloon may be
cigar-shaped, torpedo-shaped, or submarine-shaped. The balloon may
be any shape suitable for occluding one or more arteries (e.g.,
renal arteries). Non-limiting examples of balloon shapes include
spherical, ellipsoidal, cylindrical, an n-sided prism (pentagonal
or hexagonal) where n is any number, conical, and pyramidal.
[0185] In some embodiments, one or more balloons of the device may
be inflatable. Inflation of the balloon may expand the balloon to
occlude the artery. In some embodiments having two or more
balloons, the balloons may be fluidly-connected, and may be
inflated together. In other embodiments, the balloons may not be
fluidly connected, and may be capable of independently inflating.
In some embodiments, the balloons may be fluidly connected, wherein
a fluid connection may be opened or closed as needed, thereby
allowing inflation of two or more balloons together or inflation of
each balloon separately. Any number of balloons may be used. A
device of the present disclosure may have a single balloon. A
device of the present disclosure may have two or more balloons.
Non-limiting examples of a multi-balloon device include a device
comprising 2 balloons, 3 balloons, 4 balloons, 5 balloons, 6
balloons, 7 balloons, 8 balloons, 9 balloons, 10 balloons, and more
than 10 balloons. In some embodiments, one or more balloons of the
device may be inflated, and the inflation of the balloon may be
synchronized with an injection of a contrast dye (e.g., Urografin)
into the subject. In some embodiments, the contrast dye injection
may be performed prior to inflating the one or more balloons in the
device. In some embodiments, the contrast dye injection may be
performed simultaneously with the inflation of the one or more
balloons in the device. In some embodiments, the one or more
balloons in the device may be inflated prior to or after injection
of the contrast dye into the subject.
[0186] FIGS. 29A-29D show an embodiment of a position indication
feature 2900 which can be used to determine if a balloon catheter
device occludes the orifices of an artery such as the renal
arteries. The renal arteries are not shown for simplicity. FIGS.
29A-29B depict an axial view along the aorta 2950, for example an
abdominal, depicting the relative positions of the first 102 and
second 103 catheter balloons in the initial position (FIG. 29A) and
the "protective" or inflated position (FIG. 29B). FIGS. 29C and 29D
show the position indication feature 2900 in the initial position
(FIG. 29C) and the "protected" or expanded position (FIG. 29D). The
position indication feature 2900 may be used to help identify the
position of the catheter within the abdominal aorta 2950 and/or
whether of or not the renal arteries have been occluded upon
expansion of the first and second balloons 102, 103. The position
indication feature 2900 may for example comprise one or more
radio-opaque longitudinal markers as shown. The radio-opaque
longitudinal markers may be observed or monitored within the
abdominal aorta during positioning of the occlusive element (e.g.
first and second balloons 102, 103) within the abdominal aorta 2950
using x-ray imaging and used to guide positioning of the occlusive
element adjacent the renal arteries and/or confirm occlusion of the
renal arteries. When unexpanded during positioning (FIGS. 29A,
29C), the radio-opaque longitudinal markers may appear straight
within the abdominal aorta 250. Expansion of the balloons 102, 103
and occlusion of the renal arteries may confirmed by the appearance
of a bowed section, or "nipple", in the radio-opaque longitudinal
markers. FIG. 29D shows "nipples" 2901 and 2902 which may be used
as artery (e.g., renal artery) orifice locators. Such "nipples"
2901, 2902 may be formed when the balloons 102, 103 are expanded
and the flexible outer surface of the balloons 102, 103 curve to
partially enter and occlude the left and right renal artery ostia.
In the initial, unexpanded configuration (FIGS. 29A and 29C), the
radio-opaque longitudinal markers 2900 are straight; and in the
protective, expanded position (FIGS. 29B and 29D), the outer most
radio-opaque longitudinal markers 2900 are curved outwardly at the
renal arteria ostia.
[0187] Alternatively or in combination, at least a portion of the
catheter, first balloon 102, second balloon 103, or a combination
thereof may comprise a radio-opaque material or radio-opaque marker
thereon as described herein. Alternatively or in combination, one
or more of the balloons may be inflated with a radio-opaque
material as described herein. Similar bowing (e.g. "nipple"
formation) may be observed with a balloon made of or inflated with
a radio-opaque material for example.
[0188] FIG. 30 shows an X-Ray image of the device 2800 of FIGS.
28A-28C comprising a first balloon 102 and a second balloon 103
inserted into a subject, with the balloons 102, 103 expanded to be
in the "protective" or occlusive position. Arrows identify
"nipples" 2901 and 2902 which indicated that the expanded balloons
102, 103 have occluded the renal arteries as described herein. For
example, the balloons 102, 103 may be inflated with a radiopaque
fluid such that the formation of the "nipples" 2901 and 2902 are
visible in X-Ray. In cases where the balloons 102, 103 are expanded
with a non-radiopaque fluid such as carbon dioxide or saline, the
formation of the "nipples" 2901 and 2902 may be indicated by
observing the shape of radio-opaque longitudinal markers, such as
those described in FIGS. 29C-29D, on the surface of the balloons
102, 103.
[0189] FIG. 31 shows an embodiment of a time-delayed release
mechanism 3100 configured to automatically collapse the occlusive
element after a pre-determined amount of time following deployment.
Any of the devices described herein may further comprise a
time-delayed release mechanism 3100. The time-delayed release
mechanism 3100 may be configured to facilitate expansion and
subsequent collapse any of the expandable occlusive elements
described herein after a pre-determined amount of time following
deployment or expansion of the occlusive element. For example, the
time-delayed release mechanism 3100 may be used to automatically
collapse an expandable mesh braid or deflate a balloon after a
pre-determined amount of time. The time-delayed release mechanism
may, for example, comprise an energy accumulation and storage
component and a time-delay component. For example, the time-delayed
release mechanism may comprise a spring with a frictional damper.
The energy accumulation and storage component may for example be a
spring or spring-coil or the like. The time-delayed release
mechanism 3100 may for example comprise a syringe 3110 and a spring
3120 disposed around a syringe pump 3130. The tip 3150 of the
syringe 3110 may be configured to attach to the distal end of the
catheter device (not shown), for example via a press-fit,
screw-fit, or luer-lock connector. The release mechanism 3100 may
further comprise a handle 3140 which the user may grip while
depressing the syringe pump 3130 and attached spring 3120 into the
syringe 3110 to expand the occlusive element (not shown). Actuation
of the syringe pump 3130 may, in the case of a balloon catheter for
example, force a fluid (e.g. liquid or gas) into the balloon(s) via
the tip connection 3150 to the catheter device in order to inflate
and expand the balloon(s) to an expanded configuration. Removal of
the pressure applied to the syringe pump 3130 may cause the spring
3120 to release the energy it accumulated by being depressed and
quickly retract the syringe pump 3130 from its depressed position
within the syringe 3110 to deflate and collapse the balloon after a
pre-determined amount of time. Actuation of the syringe pump 3130
may, in the case of the braided mesh, cause an inner shaft to
translate relative to an outer shaft of the catheter as described
herein in order to deploy (e.g. expand) the expandable mesh braid
to an expanded configuration. Removal of the pressure applied to
the syringe pump 3130 may cause the spring 3120 to release the
energy it accumulated by being depressed and quickly retract the
syringe pump 3130 from its depressed position within the syringe
3110 to collapse the expandable mesh brain after a pre-determined
amount of time. The time-delayed release mechanism 3120 may further
comprise a frictional damper configured to introduce the
pre-determined amount of time between the inflation of the balloon,
release of the syringe pump 3130, and the release of energy by the
spring 3120. It will be understood by one of ordinary skill in the
art that the amount of friction applied by the damper to the
syringe pump 3130 and/or spring 3120 may be calibrated to generate
any pre-determined time-delay desired such as by providing the
spring 3120 with various spring constants depending on the
time-delay desired.
[0190] The time-delayed release mechanism 3100 may for example be
adjustable by one or more of the user, the manufacturer, or both.
The time-delayed release mechanism 3100 may further comprise a
synchronization component to synchronize the injection of a
contrast media or other harmful agent with the opening or closing
of the catheter shaft device as described herein. For example,
injection may be synchronized with occlusion of the renal arteries
by the first and second balloons or the expandable mesh braid such
that a contrast media may be prevented from entering the renal
arteries.
[0191] FIG. 32 shows a further embodiment of the present disclosure
including the prototype 2800 of FIGS. 28A-28C and the time-delayed
release mechanism 3100 of FIG. 31. The catheter device 2800 may
comprise a catheter 101 with a first balloon 102 and a second
balloon 103 on a proximal portion thereof as described herein. A
distal portion 3200 of the catheter 101 may comprise a connection
element 3210 configured to connect to the tip 3150 of the
time-delayed release mechanism 3100. The distal portion 3200 of the
catheter 101 may be configured to remain external to the subject
when the first and second balloons 102, 103 are positioned adjacent
the renal arteries of the subject. The catheter 101 and the syringe
3110 may be fluidly connected, for example to allow a fluid to pass
from the syringe 3110 to the catheter 101 and into the balloons
102, 103 via the catheter 101. Actuation of the time-delayed
release mechanism 3100 may expand the balloons 102, 103 with the
fluid as described herein. The distal portion 3200 of the catheter
101 may comprise one or more infusion port 3220 as described
herein. The infusion port 3220 may for example be configured to
infuse a medication or other fluid (e.g. normal saline) into the
aorta, for example via a side aperture in the catheter 101 (not
shown) as described herein. The distal portion 3200 of the catheter
101 may further comprise one or more orientation indication feature
3230. The orientation indication feature 3230 may be configured to
indicate the orientation of the occlusive element, in this example
the first and second balloons 102, 103, when positioned adjacent
renal artery ostia of the subject. The orientation indication
feature 3230 may for example comprise one or more of a visible
marking, a protrusion, a wing, a flag, or the like. The orientation
indication feature 3230 may be aligned with the first and second
balloons 102, 103 in a particular manner such that the orientation
of the orientation indication feature 3230 outside of the subject
may be indicative of the orientation of the first and second
balloons 102, 103 inside the subject. For example, the orientation
indication feature 3230 may comprise a pair of wings as shown which
include a first wing aligned (i.e., facing the same radially
outward direction as) with the first balloon 102 and a second wing
aligned with (i.e., facing the same radially outward direction as)
the second balloon 103. The catheter 101 may be sufficiently stiff
such the orientation indication feature 3230 maintains alignment
with the balloons 102, 103 as the catheter 101 is torqued or
rotated. For example, the orientation indication feature 3230 may
be configured to lie approximately parallel to (or alternatively
face perpendicularly away from or towards, or be otherwise oriented
in relation to) the ground when the first and second balloons 102,
103 are properly positioned within the abdominal aorta adjacent the
renal arteries of the subject. It will be understood by one of
ordinary skill in the art that any of the catheter devices
described herein may be attached to a time-delayed release
mechanism 3100, comprise one or more infusion port 3220, and/or
comprise one or more orientation indication feature 3230 in a
similar manner as described herein.
Example 1: Effects of Total Volume Versus Instantaneous
Concentration on Contrast Dye-Induced Nephropathy
[0192] In order to test that contrast media toxicity to kidneys is
determined more by influx contrast media concentration and not by
total amount of contrast media itnroduced, Sprague-Dawley (SD) rats
were either given bolus injections or continuously infused with
Urografin radiographic agent to deliver a same total dose of 20
milligrams (mg) of agent per kilogram (kg) of body weight
(LD.sub.50=20 mg/kg). Urografin was administered intra-arterially
over a period of 20 minutes (e.g., either 4 equal bolus injections
or a continuous infusion at a lower concentration). SD rats
receiving a bolus injection (e.g., a current standard for
administering a radiographic agent) represented a control group,
while SD rats receiving continuous administration (e.g., simulating
the effects of kidney protection with balloon-catheter renal artery
occlusion) represented the test group. Mortality was measured at 5
hours and 24 hours following administration of the radiographic
agent. Tissue biopsies were obtained, and nephropathy was assessed
5 hours following administration of the radiographic agent by
measuring the increase in serum creatine over baseline serum
creatine.
[0193] SD rats receiving the bolus administration of radiographic
agent exhibited about 30% and 75% mortality rate 5 hours and 24
hours following administration of the agent, respectively. In
contrast, SD rats receiving the continuous administration of
radiographic agent (e.g., at a lower concentration as compared to
the bolus injection) exhibited about 8% and 33% mortality rate 5
hours and 24 hours following administration of the agent,
respectively. Continuous administration of the radiographic agent
at lower concentrations yielded about a 73% and 56% reduction in
mortality rate 5 hours and 24 hours following administration of the
agent, respectively, as compared to administration using a bolus
injection. Furthermore, only about 10% of SD rats receiving the
bolus administration of radiographic agent were free of contrast
nephropathy 5 hours following administration of the agent, as
compared to 30% of SD rats receiving the continuous administration
of radiographic agent (e.g., at a lower concentration as compared
to the bolus injection). Overall, delivery of the same total dose
of radiographic agent at a lower concentration rate reduced kidney
toxicity and injury.
Example 2: Balloon Catheter Shape Affects Renal Artery
Occlusion
[0194] Branching arterial geometry and branching patterns from the
abdominal aorta vary across the patient population. To determine
the variability across the patient population, approximately 400
Chinese patients were screened, with 30 patients selected for
enhanced CT screening. The results of the screening are provided
below in Tables 1 and 2. Results are shown as mean.+-.standard
deviation (STD). Table 1 shows demographic information for the 30
patients selected for enhanced CT screening. Table 2 shows the
variation in the diameters of the supra-renal aorta, renal aorta,
and infra-renal aorta for the 30 patients selected for contrast
enhanced CT screening.
TABLE-US-00001 TABLE 1 Demographic information of the patient
population Height Weight Body Surface Area (cm) (kg) (mm.sup.2) Age
Gender Mean (mm) 163.9 57.7 1.58 64.3 19M/11F STD (mm) 7.7 12.7
0.16 15.4
TABLE-US-00002 TABLE 2 Patient variation in the geometry of the
supra-renal, renal, and infra-renal aorta Supra-renal Infra-renal
aorta Renal aorta aorta (mm) (mm) (mm) Mean 20.4 18.3 19.0 16.9
17.4 16.1 (mm) STD 2.2 2.2 2.1 2.3 2.9 2.4 (mm)
[0195] In addition to the geometry of the orifice of the
supra-renal, renal, and infra-renal aorta, the branching pattern of
the renal arteries also varied across patients. The angle at which
the renal arteries branched (as viewed along the axial plane within
the abdominal aorta) was equated to the hours on a clock face with
6 o'clock facing anteriorly (or towards the front of the subject)
and 12 o'clock facing posteriorly (or towards the back of the
subject). In a group of 24 selected patients, the right renal
artery was positioned at 9 o'clock, 10 o'clock, and 11 o'clock in
11 patients, 12 patients, and 1 patient, respectively.
Additionally, in the same group of 24 patients, the left renal
artery was positioned at 2 o'clock, 3 o'clock, and 4 o'clock in 1
patient, 20 patients, and 3 patients, respectively. Due the
variability in arterial geometry and branching patterns, we
hypothesized that the shape of the catheter balloon can affect
renal occlusion.
Example 3: Effects of Renal Artery Occlusion (e.g., Renal Cell
Ischemia) on Kidney Cell Viability
[0196] Cell samples were prepared by differentiating induced
pluripotent stem cells into nephrons. Cells were cultured for 4
days post-differentiation, changing media every 3 days, before
performing experiments. Samples were either cultured under standard
conditions or under ischemic conditions for up to 24 hours. At
periods of 1 minute, 5 minutes, 30 minutes, 5 hours and 24 hours,
the samples were incubated in Hoeschst 33342 to indicate cell
nuclei. Cells were imaged using the INCell Analyzer2200, and images
were analyzed to quantify the total number of cells and plotted as
a percentage of total cells normalized to control, where each data
point was obtained from three biological replicates. An increase in
Hoechst 33342 signal represented an increase in cell viability.
[0197] The viability of cells cultured under standard conditions
was not significantly different than the viability of cells
cultured under ischemic conditions (either reduced oxygen or
oxygen-free) up to 1 hour. These results suggest that shorter
periods (e.g., seconds) of renal artery occlusion (e.g., renal cell
ischemia) do not have an adverse effect on cell viability.
[0198] While preferred embodiments of the present disclosure have
been shown and described herein, it will be obvious to those
skilled in the art that such embodiments are provided by way of
example only. It is not intended that the invention be limited by
the specific examples provided within the specification. While the
invention has been described with reference to the aforementioned
specification, the descriptions and illustrations of the
embodiments herein are not meant to be construed in a limiting
sense. Numerous variations, changes, and substitutions will now
occur to those skilled in the art without departing from the
invention. Furthermore, it shall be understood that all aspects of
the invention are not limited to the specific depictions,
configurations or relative proportions set forth herein which
depend upon a variety of conditions and variables. It should be
understood that various alternatives to the embodiments of the
invention described herein may be employed in practicing the
invention. It is therefore contemplated that the invention shall
also cover any such alternatives, modifications, variations or
equivalents. It is intended that the following claims define the
scope of the invention and that methods and structures within the
scope of these claims and their equivalents be covered thereby.
* * * * *
References