U.S. patent application number 14/065208 was filed with the patent office on 2014-05-01 for method for reducing myocardial infarct by application of intravascular hypothermia.
The applicant listed for this patent is ZOLL Circulation, Inc.. Invention is credited to Michael W. Dae, Wade A. Keller, Timothy R. Machold.
Application Number | 20140121735 14/065208 |
Document ID | / |
Family ID | 22621441 |
Filed Date | 2014-05-01 |
United States Patent
Application |
20140121735 |
Kind Code |
A1 |
Dae; Michael W. ; et
al. |
May 1, 2014 |
Method for Reducing Myocardial Infarct by Application of
Intravascular Hypothermia
Abstract
Methods and apparatus for preventing myocardial infarction, or
lessening the size/severity of an evolving myocardial infarction,
by cooling at least the affected area of the myocardium using an
intravascular heat exchange catheter. The heat exchange catheter
may be inserted into the vasculature (e.g., a vein) and advanced to
a position wherein a heat exchanger on the catheter is located in
or near the heart (e.g., within the vena cava near the patient's
heart). Thereafter, the heat exchange catheter is used to cool the
myocardium (or the entire body of the patient) to a temperature
that effectively lessens the metabolic rate and/or oxygen
consumption of the ischemic myocardial cells or otherwise protects
the ischemic myocardium from undergoing irreversible damage or
infarction.
Inventors: |
Dae; Michael W.; (Belmont,
CA) ; Keller; Wade A.; (San Jose, CA) ;
Machold; Timothy R.; (Moss Beach, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ZOLL Circulation, Inc. |
Sunnyvale |
CA |
US |
|
|
Family ID: |
22621441 |
Appl. No.: |
14/065208 |
Filed: |
October 28, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12415984 |
Mar 31, 2009 |
8568464 |
|
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14065208 |
|
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|
10933979 |
Sep 2, 2004 |
7510569 |
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12415984 |
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|
09735314 |
Dec 12, 2000 |
6811551 |
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10933979 |
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60170831 |
Dec 14, 1999 |
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Current U.S.
Class: |
607/106 |
Current CPC
Class: |
A61F 7/123 20130101;
A61F 7/12 20130101; A61F 2007/0076 20130101; A61M 25/1002 20130101;
A61F 2007/0056 20130101; A61F 2007/126 20130101 |
Class at
Publication: |
607/106 |
International
Class: |
A61F 7/12 20060101
A61F007/12 |
Claims
1. A method of limiting or preventing infarction of myocardial
tissue in a patient who is suffering from cardiac ischemia, said
method comprising the steps of: (A) inserting a heat exchange
catheter into the vasculature of the patient; (B) using the heat
exchange catheter to lower the patient's body temperature to a
hypothermic temperature; (C) maintaining the hypothermic
temperature for a period of time; and (D) causing or allowing the
patient's body temperature to return to normothermia.
2. A method according to claim 1 wherein the organ or tissue is
cooled to a temperature below 37.degree. C. but not below
30.degree. C.
3. A method according to claim 1 wherein the organ or tissue is
cooled to a temperature below 37.degree. C. but not below
32.degree. C.
4. A method as in claim 1 wherein the organ or tissue is cooled to
a temperature below 37.degree. C. but not below 34.degree. C.
5. A method according to claim 1 wherein the hypothermic
temperature is maintained until the cardiac ischemia has been
alleviated.
6. A method according to claim 5 wherein the hypothermic
temperature is maintained until the cardiac ischemia has been
alleviated by one or more ischemia-alleviating treatment selected
from; a) administration of anti-ischemic medication; b) performance
of angioplasty, stenting, atherectomy or other catheter-based
coronary intervention and c) performance of coronary artery bypass
or other coronary revascularization surgery.
7. A method according to claim 1 wherein the heat exchange catheter
is positioned to cool blood flowing through the subject's inferior
vena cava.
8. A method according to claim 1 wherein the heat exchange catheter
is positioned to cool blood flowing through the subject's superior
vena cava.
9. A method according to claim 1 wherein Step B comprises cooling
the entire body of the subject.
10. A method according to claim 1 wherein the heat exchange
catheter has an elongate catheter shaft and a heat exchange region
located on a portion of the catheter shaft that becomes inserted
into the patient's vasculature.
11. A method according to claim 10 wherein the heat exchange region
has a helical configuration.
12. A method according to claim 10 wherein the heat exchange region
has a bellows-shaped surface.
13. A method according to claim 10 wherein the heat exchange region
has a right spiral region, a left spiral region and a bellows
shaped region located between the right spiral region and left
spiral region.
14. A method according to claim 10 wherein the heat exchange region
comprises a heat exchange balloon through which heat exchange fluid
is circulated.
15. A method according to claim 14 wherein the heat exchange
balloon has a helical configuration.
16. A method according to claim 15 wherein the heat exchange
balloon comprises a plurality of tubular balloon lobes wound
helically about a portion of catheter.
17. A method according to claim 1 wherein heat exchange of about
220 Watts occurs during Step B.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of copending U.S. patent
application Ser. No. 12/415/984 filed Mar. 31, 2009, which is a
continuation of Ser. No. 10/933,979 filed Sep. 2, 2004 now issued
as U.S. Pat. No. 7,510,569, which is a continuation of U.S. patent
application Ser. No. 09/735,314 filed Dec. 12, 2000 now issued as
U.S. Pat. No. 6,811,551, which claims priority to U.S. Provisional
Patent Application Ser. No. 60/170,831 filed Dec. 14, 1999, the
entire disclosure of each such patent and patent application being
expressly incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates generally to the field of cardiac
therapy, and more particularly to the intravascular application of
hypothermia to prevent or reduce myocardial infarct resulting from
myocardial ischemia.
BACKGROUND OF THE INVENTION
[0003] When the normal blood supply a person's heart muscle is
disrupted, the person may suffer what is commonly termed a heart
attack. Heart attacks are one of the major health problems in the
world. In the United States alone there are over 1.1 million heart
attacks a year. Of those 1.1 million victims, about 250,000 die
within 1 hour. However, those that survive the initial heart attack
generally subsequently receive treatment. In fact, about 375,000 of
those heart attack victims will make it to a hospital for treatment
within 1 hour; about 637,000 will make it to a hospital for
treatment within 4 hours. Unfortunately, when treated using current
methods, heart attacks often result in serious and permanent damage
to the heart muscle. In fact, it is estimated that about 66% of the
MI patients do not make a complete recovery, but rather suffer
permanent injury to cardiac muscle cells. An effective treatment
that minimizes permanent damage to the heart as a result of the
heart attack would be of great value to these patents.
[0004] In a typical heart attack, there is a blockage in an artery
that provide blood to some of the cardiac muscle cells, so the
cells in the affected portion of the heart (termed the area at
risk) experience ischemia, or a lack of adequate blood flow. This
ischemia results in an inadequate supply of oxygen for the muscles
and inadequate removal of waste product of muscle activity such as
CO.sub.2, lactic acid or other by-products of metabolism. These
substances may therefore reach toxic concentrations and thus, in
turn, cause serious long-term consequences such as the breakdown of
the cell walls, release of toxic enzymes or the like, and
ultimately result in the death of many or all of the cardiac muscle
cells in the area at risk.
[0005] The ischemia, however, is not always permanent. In fact, if
the heart attack does not result in the immediate death of the
individual, the ischemia is generally reversed either spontaneously
or with medical intervention. If the ischemia is a result of
blockage of an artery by a blood clot, the clot may spontaneously
dissolve in the ordinary course of time due to the body's own
natural thrombolytics, and blood may again flow to the affected
area. Alternatively, medical treatment may restore blood flow. Such
medical treatments include administration of thrombolytic drugs,
such as tPA, to dissolve blood clots in the vessels of the heart to
restore blood flow, balloon angioplasty, where an interventional
cardiologist steers a catheter with a balloon on the end into the
clogged artery and inflates the balloon to open the artery,
coronary stenting, where an interventional cardiologist steers a
catheter with a stent on it into the clogged vessel and expands the
stent to place what amounts to a scaffold into the vessel with the
blockage to hold the vessel open, or coronary by-pass surgery where
a blood vessel is harvested from elsewhere in the patient's body
and is attached around a blocked coronary artery to restore blood
to the ischemic tissue distal of the blockage. These treatments may
be applied individually or in concert with one or more of the other
treatments.
[0006] Generally if the ischemic event is for a short period of
time or oxygenated blood is available to the affected tissue from
another blood supply, for example from collateral arteries or even
from blood within the heart cavity, some or all of the muscle cells
in the area at risk may survive and ultimately recover much or all
of their function. However, if the period of ischemia is long
enough and severe enough, the cardiac muscle cells in the area at
risk may in fact die as a result of the ischemic insult. The area
of dead tissue resulting from this cell death is called an infarct
and the area may be said to be infarcted.
[0007] Unlike many cells in the body, for example, skeletal muscle
cells, cardiac muscle cells do not significantly regenerate. Thus
an infarcted region of cardiac muscle cells will generally be a
permanently non-functioning portion of the patient's heart. This
will result in decreased overall heart function, which may lead to
systemic vascular insufficiency, congestive heart failure, and even
death. It is thus of great importance to minimize the amount of
infarct that results from cardiac ischemic events.
[0008] Infarct may result from heart attacks as described above,
and may also result from myocardial ischemic events as the result
of other causes and may even be predicable. For example, in
so-called beating heart by-pass surgery, the surgeon stops the
heart for short periods of time to sew grafts onto the surface of
the heart. In such a procedure, the heart is deprived of blood
during the time that circulation is stopped, and unless protected,
infarct can result from this ischemic event.
[0009] Another common interventional procedure, cardiac balloon
angioplasty, also disrupts the blood supply to part of the heart
and results in predictable ischemia. In balloon angioplasty of the
heart, an interventional cardiologist inserts a balloon catheter
into the vasculature of the heart with the balloon deflated. The
balloon is placed at a location where the interventionalist wants
to dilate the vessel, and then inflates the balloon against the
walls of the vessel. When the balloon is inflated, it fills the
vessel in question and blocks most if not all blood from flowing
through that vessel. In this way, it creates an area of ischemia
downstream from the balloon, which ischemia persists for as long as
the balloon is inflated. Although attempts have been made to
relieve this ischemia by means of catheters that allow perfusion
from one side of the balloon to the other during inflation (so
called auto-perfusion balloons), these have generally proven to be
inadequate.
[0010] It is also sometimes the case that during or after
angioplasty the dilated vessel is either dissected or goes into
spasm. If the vessel spasms shut or is dissected, the blood supply
to all the tissue vascularized by the artery in question suffers
severe ischemia and potential infarct. In such cases the patient is
generally taken to a surgical suite and open chest by-pass is
performed. Until the by-pass is successfully completed, the area at
risk remains starved of blood.
[0011] Medical practitioners have attempted to reduce the infarct
resulting from the ischemic events suffered during beating heart
surgery and angioplasty with drugs and through a technique known as
preconditioning. Drugs, for example adenosine and RheothRx, have
been tried, and although under some circumstances they may have
some effect, they have ultimately proven generally inadequate for
one reason or another.
[0012] In preconditioning, the cardiac muscle is subjected to short
periods of ischemia, for example two or three episodes of 5 minutes
of ischemia followed by reperfusion, prior to the angioplasty or
other anticipated procedure that will expose the heart to a more
prolonged ischemic event. This has been found to reduce the infarct
size resulting from the prolonged subsequent ischemia somewhat, but
is difficult to perform safely, requires a complex set-up and is an
invasive procedure. Importantly, precondition must occur well in
advance of the ischemic event. For all these reasons it is
generally not a useful procedure, and because it necessarily must
occur in advance of the anticipated ischemic event, it is
unsuitable for treating ischemia due to heart attacks that have
already occurred or are in process.
[0013] Under ordinary circumstances, the temperature of the body
and particularly that of the blood is maintained by the body's
thermoregulatory system at a very constant temperature of about
37.degree. C. (98.6.degree. F.) sometimes referred to as
normothermia. The amount of heat generated by the body's metabolism
is very precisely balanced by the amount of heat lost to the
environment. The circulating blood serves to keep the entire body
and particularly the heart, at normothermia. Deep hypothermia
(30.degree. C. or lower) has long been known to be neuroprotective,
and believed to be cardioprotective as well. More recently, the
advantage of mild hypothermia (only as low as 32.degree. C. or even
as warm as between 35.degree. C. and normothermia) to ischemic
cardiac tissue has been recognized, either before and/or during an
anticipated ischemic event such as may occur in beating heart
surgery or coronary angioplasty, during an ischemic event such as a
heart attack in progress, or soon after an ischemic event such as a
heart attack that has already occurred. No satisfactory method of
achieving this mild cardiac hypothermia in the human clinical
setting, however, has been available before this invention. In
rabbits, ice bags or ice-filled surgical gloves have been applied
directly to the heart in an open-chest procedure. This method is
clearly very invasive, clumsy and lacks control over the level of
hypothermia applied. Other attempts have been made using cooling
blankets or externally applied ice bags or iced blankets. These
methods are slow, lack adequate control over the patient
temperature, are not directed to the heart muscle and therefore are
not effective in the human clinical setting to adequately reduce
cardiac temperature, especially in obese patients.
[0014] Another method of achieving cardiac hypothermia has been
proposed, that of pericardial lavage using a two-lumen catheter,
with the distal ends of both lumens (one input and one outflow)
sealed inside the pericardial sack. A cold solution such as cold
saline is circulated within the pericardial sack to cool the heart
muscle. While this method is rapid and directed to the cardiac
muscle, it is highly invasive, requires surgical access to the
pericardial sack which generally requires either an open chest
procedure or a thoracotomy, involves piercing the pericardial sack,
and introducing superfluous fluid into the pericardial sack of a
beating heart, all with the attendant risks. If used, it requires
the full surgical suite and delicate and highly skilled surgical
technique. The surgical invasion of the pericardial sack is
generally not acceptable to practitioners.
[0015] Thus, although mild cardiac hypothermia provides protection
against infarct resulting from a cardiac ischemic event, the
existing methods of achieving cardiac hypothermia are inadequate
and unacceptable; a better method of achieving mild hypothermia of
the heart that is fast, controlled and less invasive is needed.
SUMMARY OF THE INVENTION
[0016] The present invention provides a method for inducing
controlled hypothermia of the heart, using an intravascular heat
exchange device in the nature of a catheter. The intravascular heat
exchange device is inserted into the vasculature of a mammalian
patient and is thereafter utilized to cool blood that is flowing to
the patient's heart. In this manner, hypothermia of the myocardium
is achieved. Myocardial hypothermic treatment in accordance with
this invention may be useable to prevent or lessen myocardial
infarction in patient's who are suffering from acute myocardial
ischemia. Also, the myocardial hypothermic treatment in accordance
with this invention may be useable to prevent, deter, minimize or
treat other types of damage to the myocardium such as toxic
myocardial damage that can occur during or after administration of
certain cardiotoxic drugs or exposure to cardiotoxic agents. Also,
the myocardial hypothermic treatment in accordance with this
invention may be useable to prevent, deter, minimize or treat
certain cardiac disorders such as cardiac arrhythmias and the
like.
[0017] The heart is the body's pump to pump blood throughout the
body. A normal heart pumps blood at a rate of 3 liters per minute
per square meter and the average human is 1.7 square meters, so the
average heart pumps about 5.1 liter of blood per minute for entire
life of the person. Under normal conditions, the blood is
maintained at a very constant temperature of 37.degree. C., and
this in turn keeps the heart (and the rest of the body) at a very
constant temperature of 37.degree. C. The heart temperature is
maintained by both the temperature of the arterial blood and the
venous blood, in addition to the small amount of arterial blood
that is re-circulated through the coronary arterial tree to feed
the heart muscle (estimated to be 4% of the total circulation) the
average heart pumps about 306 liters of blood per hour, blood that
is all circulated through the heart cavities. Therefore cooling the
venous blood that enters the heart will effectively cool the heart
by direct contact with the cardiac muscle in the cardiac
cavities.
[0018] As may be seen, cooling the venous blood in the vena cava
also effectively cools the arterial blood that is circulated
through the cardiac arteries. After being cooled in the vena cava,
the blood first enters the right atrium, is then pumped through the
lungs (which expose the blood to air at room temperature which is
generally less than normothermia), from whence it is returned to
the left atrium, and then to the left ventricle. The left ventricle
pumps the oxygenated blood to the body through the aorta, and the
first arteries to branch off the aorta are the coronary arteries.
Thus the blood will be circulated through the arterial tree of the
heart without ever having picked up metabolic heat from the rest of
the body. The heart is thus cooled both by direct contact with the
cooled blood and by having the cooled blood circulated through the
coronary arteries before picking up metabolic heat from the
outlying capillary beds.
[0019] Described herein is a method for reducing the size of any
infarct that results from a cardiac ischemic event by inserting a
cooling catheter having a heat exchange region into the vasculature
of a patient, placing the heat exchange region into the blood
stream flowing to the heart, cooling the blood as it passes the
heat exchange region and thus directing cooled blood to the heart
muscle before, during and/or after an ischemic event for a
sufficient length of time to reduce the temperature of the heart.
The method advantageously is practiced by placing the heat exchange
region of the catheter into the patient's vena cava, either the
inferior vena cava (IVC) or the superior vena cava (SVC), and the
heat exchange region may even be placed partially or totally within
the heart itself. The cooling catheter may be introduced into the
patient in any acceptable means, for example percutaneously through
the femoral vein into the IVC or via the internal jugular vein into
the SVC, by surgical cut-down, or by surgical placement in a
patient with an open chest.
[0020] The cooling of the cardiac muscle is advantageous if
performed after a cardiac ischemic event, for example a heart
attack, and is advantageous if performed before an anticipated
ischemic event, for example before or during coronary angioplasty
or beating heart surgery, and if performed during an ischemic
event, for example during a heart attack in progress or during an
angioplasty or beating heart surgery.
[0021] The cooling of the blood may be done by a cooling catheter
having various acceptable types of cooling regions, for example a
cooling catheter with a balloon for receiving the circulation of
heat transfer fluid that is cooled outside of the body of the
patient. Of particular value is the efficiency of a multi-lobed
heat exchange balloon. Other heat exchange elements, however, are
also useful in this method. For example, flexible metallic heat
exchange regions or heat exchange regions with multiple heat
exchange elements would be acceptable for practicing the patented
method.
[0022] While the heart may experience some harmful effects of when
subjected to very deep hypothermia such as arrhythmia's at
temperatures below 30.degree. C., profound reduction of infarct
resulting from ischemia may be experienced as a result of mild
hypothermia of only a few degrees below normothermia, for example
hypothermia as mild as 35.degree. C. or above, thereby enjoying the
benefits of hypothermia while avoiding the harmful effects of deep
hypothermia. Therefore cooling the heart to mild levels of
hypothermia above 32.degree. C. is preferred in this method. These
temperature targets, of course, will vary somewhat from patient to
patient, and from circumstance to circumstance.
[0023] Beside the level of hypothermia, the time during which the
hypothermia is administered may vary according to the
circumstances. For example, the heart may be cooled for a short
period of time and then rewarmed, or may be cooled and maintained
in a cooled condition for some period of time. For example, a heart
attack victim may have the cardiac muscle cooled for an hour, while
the hypothermia may be applied during beating heart surgery for
several hours.
[0024] The heart may also be selectively cooled. That is, the blood
directed to the heart may be cooled immediately before being
directed to the heart, for example, when the blood is in the IVC,
and the blood directed to the rest of the body after leaving the
heart may be warmed, for example by a warming catheter in the
descending aorta or warming blankets on the skin of the patient.
The method of this invention tends to result in a core body
temperature that is several degrees warmer than the cardiac
temperature achieved, at least initially, and this difference can
be accentuated and prolonged by the use of warming blankets or
other means to warm the blood of the patient after the cooled blood
has left the heart of the patient.
[0025] These and other objects and advantages of the invention can
be better understood with reference to the drawings and the
detailed description of the embodiments of the invention described
below.
BRIEF DISCRIPTION OF THE DRAWINGS
[0026] FIG. 1 is a depiction of a heat exchange catheter in the
vasculature of a patient with the heat exchange region of the
catheter located in the vena cava of the patient.
[0027] FIG. 2 is a cross-sectional view of the shaft of a heat
exchange catheter.
[0028] FIG. 3 shows a side view of the heat exchange region of a
heat exchange catheter as assembled.
[0029] FIG. 4 shows the shaft member of the heat exchange catheter
of FIG. 3.
[0030] FIG. 5 shows the balloon configuration of the catheter
assembly of FIG. 3.
[0031] FIG. 6 is a view of a portion of the heat exchange catheter
of FIG. 3 illustrating outflow of heat exchange fluid.
[0032] FIG. 7 is a view of a portion of the catheter of FIG. 3
illustrating inflow of exchange fluid.
[0033] FIG. 8 is a cross-sectional view of the shaft of FIG. 3 and
FIG. 4 taken along the line 8-8.
[0034] FIG. 9 is a cross-sectional view of the balloon of FIG. 5
taken along the line 9-9.
[0035] FIG. 10 is a cross-sectional view of the catheter of FIG. 3
taken along the line 10-10.
[0036] FIG. 11 is a cross-sectional view of the catheter of FIG. 3
taken along the line 11-11.
[0037] FIG. 12 is a cross-sectional view of the catheter of FIG. 3
taken along the line 12-12.
[0038] FIG. 13 is an illustration of a heat exchange balloon having
a spiral shaped heat exchange region in place in the IVC.
[0039] FIG. 14 is an illustration of a bellows shaped heat exchange
region in place in the IVC.
[0040] FIG. 15 is an illustration of a flexible metal heat transfer
region with spiral shaped heat transfer fins and radial heat
transfer fins on the surface of the heat exchange region, said heat
exchange region in place in the IVC.
[0041] FIG. 16 is an enlarged side view of the heat transfer region
of the catheter of FIG. 15.
[0042] FIG. 17 is a cross-sectional view of the heat transfer
region of FIG. 15.
[0043] FIG. 18. is an illustration of a heat exchange catheter
having a heat exchange region comprising multiple heat exchange
elements in place in the vena cava.
[0044] FIG. 19 is an illustration of a heat exchange catheter
inserted into a patient via an internal jugular vein insertion,
with the heat exchange region in place in the SVC.
[0045] FIG. 20 is a graph of the body temperature during cooling as
measured at different locations in the body.
[0046] FIG. 21 is a flow chart depicting the steps of the method as
described in the detailed description.
DETAILED DESCRIPTION
[0047] The present invention comprises a method of cooling the
beating heart to protect myocardial tissue from infarct as a result
of ischemia. The heart is cooled by placing a heat exchange
catheter having a heat exchange region in contact with blood
flowing to the heart, for example, blood in the IVC, cooling the
heat exchange region to a temperature lower than that of the blood,
for example circulating saline at 2.degree. C. through the heat
exchange region to cool the heat exchange region to about 2.degree.
C. thereby cooling the blood to a temperature below normothermia,
and maintaining the cooling for a long enough time to reduce the
temperature of the heart.
[0048] In intravenous cooling such as that described in the
previous paragraph, a heat exchange region is placed in the
bloodstream and maintained at a lower temperature than the blood.
The rate of cooling blood by means of a heat exchange region in
contact with flowing blood depends on a number of factors. One is
the difference in temperature between the blood and the heat
exchange region in contact with that blood. Other factors include
the specific heat of the blood, the amount of surface area of the
heat exchange region in contact with the blood, and the heat
transfer coefficient between the blood and the surface of the heat
exchange region. Certain other factors may also effect the
efficiency of heat transfer between the heat exchange region and
the colloidal fluid that is blood, such as turbulent flow (see e.g.
U.S. Pat. No. 5,624,392 to Saab, col. 11, II. 56-60) to enhance
heat exchange. Where the heat exchange region is cooled by the
circulation of heat exchange fluid, counter-current flow between
the blood and the heat exchange fluid is important so that the heat
exchange fluid flows through the heat exchange region in a
direction opposite that of the blood flow. In this way, the warm
blood flows over the warmest part of the heat exchange region first
toward the coldest part of the heat exchange region. It has been
found that a balloon heat transfer catheter of the type described
below with the heat exchange region placed in contact with blood
flowing in the IVC is a satisfactory method of practicing this
invention, although other heat exchange catheters with other types
of heat exchange regions are within the scope of the invention.
[0049] Essentially all the blood flow into the heart cavities flows
through the vena cava, the IVC below the heart and the SVC above
the heart. It is estimated that in the ordinary human 2/3 of the
total venous return to the heart flows through the IVC and 1/3
through the SVC. The vena cava is a large vessel; in the human
patient, the IVC is generally about 200 millimeters long and
generally ranges between about 160 millimeters and 260 millimeters.
In diameter it varies somewhat over that length, but averages about
21 millimeters in diameter. Cooling blood flowing through the vena
cava provides an effective way of inducing mild hypothermia to the
heart. Blood flowing through the vena cava is flowing directly to
the heart cavities. It cools the heart directly by contact with the
heart muscle. The blood that feeds the cardiac arteries would also
generally be relatively cool since blood cooled in the vena cava
travels only to the lungs before being pumped through the cardiac
arteries. In the lungs the blood is exposed to air at ambient
temperature which is usually below normothermia, and the blood does
not travel through the rest of the body where it would pick up
metabolic heat.
[0050] Because large volumes of blood are cooled by the method of
the invention, the temperature of the entire body may be somewhat
depressed, that is the patient may experience what is sometimes
called whole body hypothermia. Although it is generally the case
the body functions most efficiently at normothermia, some whole
body hypothermia is acceptable and in some situations may even by
therapeutic. In any event, as the example detailed below describes,
the temperature of the body core other than the cardiac muscle
tends to lag the hypothermia experienced by the cardiac muscle, and
this results in even shallower hypothermia than that experienced by
the cardiac muscle. It is often the case that the application of
cooling to the heart with the heat exchange region of the cooling
catheter in the vena cava tends to be fairly short, perhaps an hour
or less, so the core cooling experienced by the whole body while
practicing this method is generally not harmful.
[0051] FIG. 1 shows a heat exchange catheter 10 having a heat
exchange region 12 located in the IVC 14 of a patient. The heat
exchange region is maintained at a temperature below that of the
blood, perhaps as cold as 0.degree. C., so that blood flowing past
the heat exchange region gives off heat to the heat exchange region
and thus is cooled. The cooled blood, indicated by arrows in FIG.
1, flows into the heart 16 and cools the heart.
[0052] The balloon heat exchange catheter may be placed in the
vasculature of a patient by for example, percutaneously inserting
it using the well known Seldinger technique into the femoral vein
18 and advancing it toward the heart until the heat exchange region
12 is located the vena cava of the patient. In one preferred
method, a balloon heat exchange catheter has a heat exchange region
comprising a balloon with mechanisms for circulating cold saline
through the balloon as the heat exchange fluid. The balloon is
percutaneously placed into the femoral vein and advanced to locate
the heat exchange balloon in the IVC. As shown in FIG. 2, the shaft
18 of the heat exchange catheter has three lumens therein, an
inflow lumen 20 for the flow of heat exchange fluid to the heat
exchange region, an outflow lumen 22 for the flow of heat exchange
fluid from the heat exchange region, and a working lumen 24 that
may be used for a guide wire or the administration of medicaments
from the proximal end of the catheter through the distal end of the
catheter.
[0053] The inflow lumen is in fluid communication with the distal
end of the balloon; the outflow lumen is in fluid communication
with the proximal end of the balloon. The heat exchange fluid is
circulated from outside the body, down the inflow lumen to the
distal end of the balloon, through the balloon, and back out the
outflow lumen. In this example this results in the heat exchange
fluid flowing in the opposite direction of the blood, i.e.
counter-current flow. This counter-current heat exchange between
flowing liquids is the more efficient means of exchanging heat.
[0054] By controlling the temperature of the saline, the
temperature of the balloon may be controlled. The saline may be
cooled outside the body by, for instance, an external heat
exchanger 26, to cool the saline to as low as 0.degree. C. The
balloon is thereby cooled to as low as 0.degree. C., at least at
the point where the heat exchange fluid first begins to exchange
heat with the blood. As will be readily appreciated, a temperature
gradient is established along the length of the balloon. Where the
heat exchange fluid first enters the balloon, the balloon is at its
coldest. If the heat exchange fluid is at 7.degree. C. for example,
when it exits the central lumen and enters the balloon, the surface
of the balloon will be essentially 7.degree. C. At that point, if
the blood is at normothermic, that is 37.degree. C., the DT would
be 30.degree. C. and the blood would give off heat through the
balloon to the heat exchange fluid. It should be noted that not all
the heat exchanged between the blood and the heat exchange fluid
will be at the heat exchange region. Some heat may be exchanged
between the blood flowing in the femoral vein and the vena cava so
the temperature at the coldest point on the heat exchange region
may be as warm as 7.degree. C. even if the saline is cooled by the
external cooler to as cold as 0.degree. C. It is preferable to
exchange the maximum amount of heat in the IVC near the heart by
means of the heat exchange region, but the blood in the femoral
vein and IVC which may exchange heat with the shaft of the catheter
ultimately flow past the heat exchange region and into the heart,
so that heat exchanged by this portion of the heat exchange
catheter also serves somewhat to cool the heart. Therefore, in
evaluating the performance of the catheters used in the preferred
embodiments of this invention, the temperature at the inlet to the
heat exchange catheter, that is soon after it leaves the external
heat exchanger, and the temperature at the outlet of the heat
exchange catheter, that is just before it enters the external heat
exchanger, in conjunction with the flow rate of heat exchange fluid
in the catheter, can give a useful estimate of the heat exchanged
with the blood directed to the heart, although it would include
both the heat exchanged at the heat exchange region and heat
exchanged along the shaft. For example, in the multi-lobed heat
exchange catheter described in detail below, the temperature at the
inlet may be measured at about 4.degree. C. and the temperature at
the outlet at about 11.degree. C. The flow rate in the catheter may
be about 450 ml/min. This indicated a total heat exchange of about
220 watts of energy, a performance adequate for practicing the
method of this invention.
[0055] It should be noted that the exchange of heat from the body
may be controlled by controlling the external heat exchanger. For
example, if maximum temperature reduction were desired, maximum
power to the heat exchange region would result in the coldest
possible heat exchange fluid and thus the largest DT between the
heat exchange fluid and the blood. Once the target temperature had
been reached and the number of watts needed to be removed from the
blood to maintain the target temperature was less, the watts
transferred from the body could be reduced by reducing the power to
the external heat exchanger. This would in turn increase the
temperature of the heat exchange fluid as it left the external heat
exchanger and entered the catheter, which would decrease the DT
between the blood and the heat exchange fluid, and thus reduce the
watts removed from the bloodstream.
[0056] The external heat exchanger may be, for example, a hot/cold
plate formed of a number of thermoelectric units such as Peltier
units, or other hot or cold elements in contact with a thermal
exchange bag through which the heat exchange fluid is circulated.
If the bag is sealed and forms a closed circuit with the heat
exchange fluid in the catheter, the heat exchange fluid may be
heated or cooled exterior of the body without ever being exposed to
the air. If the saline is initially sterile, it may thereby be
maintained sterile, an advantage for fluid that is circulated
through the body. Although the heat exchange fluid is not
intentionally in contact with the blood, if a leak should occur it
would be a significant advantage to use sterile heat exchange
fluid.
[0057] The external heat exchange unit, in turn, may controlled by
controller 28 that may be pre-programmed or may be reactive to a
temperature sensor 30 that senses the temperature of the patient.
As will be readily appreciated by those of skill in the art, the
temperature sensor may sense the temperature of the heart itself to
the patient's body temperature as measured by a rectal sensor, an
esophageal sensor, a tympanic sensor or the like. It has been found
that the temperature sensors in the heart tissue when a heat
exchange balloon is located in the vena cava tends to more closely
reflect the temperature of the heat exchange balloon than do the
rectal, esophageal or tympanic sensors, but that these various
sensors correlate well with each other, and thus, with the
appropriate compensation factors, any one of them may be used to
control the temperature of the heat exchange region for purposes of
inducing and controlling cardiac hypothermia.
[0058] If the external heat exchanger is able to both heat and
cool, as is the case for example in the Peltier elements described
above, the heat exchange fluid may be heated or cooled in response
to the signal from the sensor. If the external heat exchange unit
is able to be controlled as to the amount of heating or cooling it
provides, the degree of heating or cooling supplied by the heat
exchange unit may be controlled in response to the signal received
from the sensor. As will be seen in the example described below,
this will allow the operator to cool the heart to a predetermined
temperature, maintain the heart at a predetermined temperature for
a length of time, and add heat to the blood to warm the heart at a
chosen point. In practice, the controller receives a signal that
represents the temperature of the heart tissue. As this temperature
nears the target temperature, the controller causes the external
heat exchanger to reduce the amount of cooling applied to the heat
exchanger. By internal calculations, the rate of decrease of the
temperature of the heart tissue is calculated relative to the
amount of energy applied by the external heat exchanger, and as the
heart tissue nears and finally reaches the target temperature, the
precise amount of cooling that must be applied by the external heat
exchanger to cause a rate of change of essentially 0 is known. By
application of this amount of cooling by the external heat
exchanger when the heart reaches the target temperature, the heart
is essentially maintained at precisely this temperature. In this
way, by use of the controller receiving a signal from the patient's
body that represents heart temperature, the operator is able to
precisely control the level of hypothermia applied. By determining
how long the controller will maintain this level of hypothermia and
when it will begin to re-heat, the length of the hypothermia
applied to the heart may also be precisely controlled.
[0059] Although the heat exchange region shown in FIG. 1 is a
simple, single lobed balloon, the heat exchange region may be of
various advantageous configurations. One effective catheter for
exchanging heat with the blood in the vena cava is a heat exchange
balloon catheter having a heat exchange region that is a
multi-lobed balloon and has the temperature of the heat exchange
region controlled by controlling the temperature of heat exchange
fluid circulated through the balloon.
[0060] Such a catheter is depicted in FIG. 3 through FIG. 12. The
assembled catheter 31 (FIG. 3) has a four-lumen, thin-walled
balloon 33 (FIG. 5) which is attached over an inner shaft 35 (FIG.
4).
[0061] The cross-sectional view of the four-lumen balloon is shown
in FIG. 9. The balloon has three outer lumens 37, 39, 41 which are
wound around an inner lumen 43 in a helical pattern. All four
lumens are thin walled balloons and each outer lumen shares a
common thin wall segment 42 with the inner lumen 43. The balloon is
approximately twenty-five centimeters long, and when installed,
both the proximal end 67 and the distal end 89 are sealed around
the shaft in a fluid tight seal.
[0062] The shaft 35 is attached to a hub 47 at its proximal end.
The cross section of the proximal shaft is shown at FIG. 8. The
interior of the shaft is configured with three lumens, a guide wire
lumen 49, an inflow lumen 51 and an outflow lumen 53. (For purposes
of this description the inflow lumen is lumen 51, and the outflow
lumen is 53. As one of skill in the art may readily appreciate, the
inflow and outflow lumens may be reversed if desired.) At the hub,
the guide wire lumen 49 communicates with a guide wire port 59, the
inflow lumen is in fluid communication with an inflow port 55, and
the outflow lumen is in communication with an outflow port 57.
Attached at the hub and surrounding the proximal shaft is a length
of strain relief tubing 61 which may be, for example, heat shrink
tubing.
[0063] Between the strain relief tubing and the proximal end of the
balloon, the shaft 35 is extruded with an outer diameter of about
0.118 inches. The internal configuration is as shown in
cross-section in FIG. 8. Immediately proximal of the balloon
attachment 67, the shaft is necked down 63. The outer diameter of
the shaft is reduced to about 0.100 to 0.110 inches, but the
internal configuration with the three lumens is maintained.
Compare, for example, the shaft cross-section of FIG. 8 with the
cross-section of the shaft shown in FIG. 10 and FIG. 11. This
length of reduced diameter shaft remains at approximately constant
diameter of about 0.10 to 0.11 inches between the necked down
location at 63 and the necked down location at 77.
[0064] At the necked down location 63, a proximal balloon marker
band 65 is attached around the shaft. The marker band is a
radiopaque material such as a platinum or gold band or radiopaque
paint, and is useful for locating the proximal end of the balloon
by means of fluoroscopy while the catheter is within the body of
the patient.
[0065] At the marker band, all four lobes of the balloon are
reduced down and fastened to the inner member 67. This may be
accomplished by folding the balloon down around the shaft, placing
a sleeve, for example a short length of tubing, over the balloon
and inserting adhesive, for example by wicking the adhesive, around
the entire inner circumference of the sleeve. This simultaneously
fastens the balloon down around the shaft and creates a fluid tight
seal at the proximal end of the balloon.
[0066] Distal of this seal, under the balloon, an elongated window
73 is cut through the wall of the outflow lumen in the shaft. Along
the proximal portion of the balloon, five slits, e.g. 75, are cut
into the common wall between each of the outer balloon lumens and
the inner lumen 43. (See FIG. 10 and FIG. 6.) Because the outer
lumens are twined about the inner lumen in a helical fashion, each
of the outer tubes passes over the outflow lumen of the inner shaft
member at a slightly different location along the length of the
inner shaft, and therefore an elongated window 73 is cut into the
outflow lumen of the shaft so that each outer lumen has a cut 75
where that lumen passes over the window in the shaft. Additionally,
there is sufficient clearance between the outer surface of the
shaft and the walls of the inner lumen 43 to create sufficient
space to allow relatively unrestricted flow through the 5 slits 75
in each outer lumen 37,39,40 to the outflow lumen of the shaft
53.
[0067] Distal of the elongated window in the outflow lumen, the
inner member 43 of the four-lumen balloon is sealed around the
shaft in a fluid tight seal 82. The outflow lumen is plugged 79,
and the wall to the inflow lumen is removed. (See FIG. 11.) This
may be accomplished by necking down the shaft 77 to seal the
outflow lumen shut 79, removing the wall of the inflow lumen 81,
piercing a small hole in the wall of the inner lumen 84 and wicking
UV curable adhesive into the hole and around the entire outside of
the shaft, and curing the adhesive to create a plug to affix the
wall of the inner lumen of the balloon around the entire outside of
the shaft 83. The adhesive will also act as a plug to prevent the
portion of the inner lumen proximal of the plug from being in fluid
communication with the inner member distal of the plug.
[0068] Just distal of the necked down location 77, the guide wire
lumen of the shaft may be terminated and joined to a guide wire
tube 87. The guide tube then continues to the distal end of the
catheter. The inflow lumen 81 is open into the inner lumen of the
four-lobed balloon and thus in fluid communication with that
lumen.
[0069] The distal end of the balloon 89 including all four lumens
of the balloon is sealed down around the guide wire tube in a
manner similar to the manner the balloon is sealed at the proximal
end around the shaft. This seals all four lumens of the balloon in
a fluid tight seal. Just proximal of the seal, four slits slits 91
are cut each the common wall between each of the three outer lumens
37, 39, 41 of the balloon and the inner lumen 43 so that each of
the outer lumens is in fluid communication with the inner lumen.
(See FIG. 5 and FIG. 12.)
[0070] Just distal of the balloon, near the distal seal, a distal
marker band 93 is placed around the inner shaft. A flexible length
of tube 95 may be joined onto the distal end of the guide wire tube
to provide a flexible tip to the catheter. Alternatively, a soft
tip 98 may be attached over the very distal end of the catheter.
The distal end of the flexible tube 97 is open so that a guide wire
may exit the tip, or medicine or radiographic fluid may be injected
distal of the catheter through the guide wire lumen.
[0071] In use, the catheter is inserted into the body of a patient
so that the balloon is within a blood vessel. Heat exchange fluid
is circulated into the inflow port 55, travels down the inflow
lumen 51 and into the inner lumen 43 at the end of the inflow lumen
81. The heat exchange fluid travels to the distal end of the inner
lumen and through the slits 91 between the inner lumen 43 and the
outer lumens 37, 39, 41.
[0072] The heat exchange fluid then travels back through the three
outer lumens of the balloon to the proximal end of the balloon. The
outer lumens are wound in a helical pattern around the inner lumen.
At some point along the proximal portion of the shaft, each outer
lumen is located over the portion of the shaft having a window to
the outflow lumen 76, 74, 73, and the outer balloon lumens have
slits 75, 78, 80 that are aligned with the windows. The heat
transfer fluid passes through the slits 75, 78, 80 through the
windows 73, 74, 76 and into the out flow lumen 53. From there it is
circulated out of the catheter through the outflow port 57. At a
fluid pressure of 41 pounds per square inch, flow of as much as 500
milliliters per minute may be achieved with this design.
[0073] Counter-current circulation between the blood and the heat
exchange fluid is highly desirable for efficient heat exchange
between the blood and the heat exchange fluid. Thus if the balloon
is positioned in a vessel where the blood flow is in the direction
from proximal toward the distal end of the catheter, for example if
it were placed from the femoral vein into the ascending vena cava,
it is desirable to have the heat exchange fluid in the outer
balloon lumens flowing in the direction from the distal end toward
the proximal end of the catheter. This is the arrangement described
above. It is to be readily appreciated, however, that if the
balloon were placed so that the blood was flowing along the
catheter in the direction from distal to proximal, for example if
the catheter was placed into the IVC from a jugular insertion, as
is illustrated in FIG. 8, it would be desirable to have the heat
exchange fluid circulate in the outer balloon lumens from the
proximal end to the distal end. Although in the construction shown
this is not optimal and would result is somewhat less effective
circulation, this could be accomplished by reversing which port is
used for inflow direction and which for outflow.
[0074] As depicted in FIG. 13, a catheter such as that described
above, with the heat exchange region 99 located in the IVC provides
an advantageous apparatus for the practice of the method of this
invention. Other advantageous configurations for the heat exchange
region may be employed, however. For example, the heat exchange
region may have a bellows-shaped surface 100 as shown in FIG. 6, or
the heat exchange region 102 may have a surface shaped with
alternating right handed spirals 104 and left handed spirals 106
with a bellows shaped surface 108 between the spirals as shown in
FIGS. 14-17. Another acceptable variation of the heat exchnge
catheter would have a heat exchange region 110 comprising multiple
heat exchange elements 112 as illustrated in FIG. 18.
[0075] Those of skill in the art will also readily appreciate that,
beside the use of different heat exchange regions, other acceptable
placements of the heat exchange region may be employed to practice
the method of this invention. For example, An internal jugular
insertion may be made wherein the catheter is inserted into the
internal jugular vein 120 and the heat exchange region advanced to,
for example, the SVC 122 as illustrated in FIG. 8. With an internal
jugular insertion, if the heat exchange region is only advanced
into the SVC, the blood flow will be from the proximal to the
distal end of the heat exchange region, i.e. in the same relative
direction as with a femoral insertion and placement of the heat
exchange region in the IVC, so counter-current flow between the
heat exchange fluid and the blood will be maintained with the same
catheter as described above.
EXAMPLE
[0076] The method of the invention may be described by reference to
the following example. In the instance described here, the cardiac
cooling method of the invention was performed using 60 B 80 kg.
pigs. The study was conducted in accordance with The Guide for Care
and Use of Laboratory Animals. Each pig was anesthetized with
isoflourane anesthesia, and vascular sheaths were inserted
percutaneoulsy in to the femoral artery and vein respectively. A
median sternotomy was done, followed by the isolation of the left
anterior descending coronary artery. A three lobed heat exchange
catheter as described above was inserted into the sheath in the
femoral vein and the catheter was advanced until the heat exchange
region was in the IVC just below the heart. Saline was circulated
through the heat exchange region of the catheter and an exterior
heat exchanger. The exterior heat exchanger was in the form of a
hot/cold plates formed by a number of Peltier units, and a bag of
saline in contact with the plates. The circuit of the saline
through the bag and through the catheter including the heat
exchange region was closed, and the saline was sterile. The
temperature of the Peltier plates, and thus of the saline, was
controlled by a lap-top computer using a commercially available
control program readily available to and understood by those of
skill in the art, and was controlled in response to core
temperature sensed by an esophageal temperature sensor of the type
typically used in the medical arts.
[0077] The core temperature was initially maintained at 38.degree.
C. (normothermia for pigs) by adding or removing heat as necessary
with the heat exchange catheter. Because the chest had been opened
by the sternotomy, this generally comprised adding a small amount
of heat to the blood. The left anterior descending coronary artery
was occluded for a total of 60 minutes about 2/3 of the way down
its length using a snare. The snare was formed using a suture
placed around the descending coronary artery, with both legs of the
suture contained within a plastic tube. The snare was tightened and
the occlusion formed by sliding the tube down against the
artery.
[0078] Twenty minutes into the occlusion, the external heat
exchanger was turned on with the controller was set to remove heat
via the heat exchange catheter to lower the cardiac temperature of
the pig at the maximum rate. Heat was removed from the blood
flowing through the IVC at a rate that varied somewhat between test
animals from about 140 watts to 220 watts, but was generally about
190 watts.
[0079] At the end of the 60-minute period of ischemia, the snare
was loosened by removing the plastic tube by sliding it away from
the artery and off the suture. The removal of the snare restored
flow to (re-perfused) the ischemic area. The suture was left, lose
but in place around the artery. Cooling in order to maintain the
target temperature of 34.degree. C. was maintained for 15 minutes
after the removal of the occlusion. In the pigs receiving
hypothermia, there was thus a total of 55 minutes of cooling:
beginning after 20 minutes of occlusion; 40 minutes of cooling
during occlusion; then 15 more minutes of cooling after
re-perfusion.
[0080] After the period of cooling (55 minutes) the external heat
exchanger was switched to begin heating, and the temperature of the
saline circulating through the heat exchange catheter was raised to
41.degree. C. This in turn began warming the blood and rewarming
the pig toward normothermia.
[0081] The control pigs were maintained at normothermia (38.degree.
C.) initially and during occlusion, and this temperature was
maintained for an additional three hours after reperfusion. In the
hypothermic pigs, re-warming toward 38.degree. C. was allowed to
occur for 2 hours and 45 minutes, that is also until three hours
after reperfusion. At the end of this period (4 hours after the
initial occlusion), the suture was again tied off around the artery
to occlude the vessel, and monastral blue dye was injected into the
left ventricular cavity to define the ischemic area at risk. The
dye stained all the areas of the heart that were vascularized, and
since the suture was tied off around the cardiac artery at the same
location as originally occluded, the area at risk would be
unstained and would visually accurately define the area at risk
during the original ischemia.
[0082] The heart was harvested to analyze the effect of the
hypothermia on infarct resulting from the ischemic event. The heart
was excised, sliced into 0.5 to 1.0 cm slices, and the slices were
immersed into 1% triphenyltetrazolium chloride (TTC) for 15 minutes
to stain the viable tissue. Nonviable tissue is not stained by TTC.
The myocardial slices were photographed using a digital camera and
the area at risk, and the infarction zones were quantified using
image analysis software. Six animals were studied with hypothermia,
while an additional six animals served as controls. For the
controls, the heat exchange catheter was placed into the IVC and
the controller set to maintain the esophageal temperature
38.degree. C. Otherwise, the procedure was identical for the
experimental hypothermia animals and the controls. Results below
are expressed as 1) Area at risk (AAR), and 2) Percent of AAR that
suffered infarct.
Results:
TABLE-US-00001 [0083] HYPOTHERMIC CONTROL AAR IF/AAR AAR IF/AAR Pig
# (% LV) (% AAR) Pig # (% LV) (% AAR) 1 11.3 0.0 1 25.4 49.1 2 13.6
0.0 2 12.6 35.9 3 11.2 0.0 3 14.9 44.8 4 21.1 0.8 4 33.6 45.1 5
18.2 0.0 5 17.7 61.5 6 23.7 12.8 6 10.4 47.0 Mean .+-. 16.6 .+-.
2.3 .+-. Mean .+-. 19.1 .+-. 47.2 .+-. SD 5.3 5.3 SD 8.8 8.3 P
Value P = P < Hypothermic vs. NS 0.000005 Normothermic
[0084] It should be noted that the core temperature of the pig as
measured by the tympanic or rectal probe never reached as low a
temperature as did the heart itself. A graph showing the
temperatures as measured at different locations during one
experiment is depicted in FIG. 20. The cardiac temperature was
measured by temperature sensors located in the muscle of the left
ventricle and of the left atrium. Temperatures were also measured
by sensors in the rectum, in the eardrum (tympanic) and in the
esophagus. All of the temperatures measured away from the heart
itself tended to lag the cardiac temperature, sometimes as much as
2.degree. C. Presumably the fact that the heart was contacted with
the cool blood first, and even warmed that blood somewhat before it
went out to other locations would explain this difference.
[0085] If the heart had reached a target temperature, and the rate
of cooling had been reduced to only that necessary to maintain that
target temperature, the rate at which the rest of the body would
have approached equilibrium would have slowed considerably, and the
core body temperature as measured away from the heart would have
continued to lag. Presumably, however the body would ultimately
reach equilibrium at some hypothermic temperature.
[0086] This, however, would take a long time, and in the time while
the heat exchange catheter was cooling the heart at hypothermic
temperature, the body temperatures never reached equilibrium. Once
the heat exchange catheter began to warm the blood, the entire body
began to experience warming, and therefore the body core away from
the heart never experienced hypothermia as deep as that experienced
by the heart. For the times involved in the hypothermic treatment
of the method, and for the depth of hypothermia involved, the whole
body cooling that resulted was within acceptable limits.
[0087] In humans, the same method of applying hypothermia can be
used to reduce infarct resulting from an ischemic event. A
multi-lobed balloon catheter such as that described above, may be
percutaneously placed through the femoral vein so that the heat
exchange region is located in the IVC or through the internal
jugular vein so that the heat exchange region is located in the
SVC, and the blood therein cooled by cooling the heat exchange
region (the balloon) by circulating cold saline through the cooling
catheter. Saline at about 0.degree. C. can be circulated without
undue damage to the blood. A controller receiving a signal
representing cardiac temperature, either directly or through some
surrogate such as esophageal or tympanic temperature, can control
the heat exchange catheter to achieve a target temperature and
maintain that temperature. As was the case with the pigs, the heat
removed from the blood also results in overall temperature
reduction in the whole body since the body is unable to generate
sufficient heat to replace that amount removed by the heat exchange
catheter, but the heart tends to cool more rapidly than that of the
rest of the body. The whole body cooling may be desirable in some
instances for therapeutic reasons, for example for neuroprotection
is some global ischemia is experienced, but at least at the mild
levels of hypothermia in the method of the invention, and for the
time lengths expected, therapeutic hypothermia of the heart is
obtained by this technique without undue injury to the patient. It
is anticipated that means to inhibit shivering using drugs such as
meperidine, Thorazine, Demerol, phenegran or combinations thereof,
or applying heat to the skin surface may be necessary to prevent or
reduce shivering in unanesthesized patients receiving hypothermic
therapy.
[0088] The method of the invention is described in the flow chart
of FIG. 21. In Step 1, the heat exchange catheter is inserted into
the vasculature of a patient. This is typically inserted
percutaneously into the femoral vein, but may also be inserted into
the internal jugular vein, or in any other suitable fashion
depending on the circumstances. For example, if the patient is in
surgery, insertion by a cut-down may be preferable. If access to
the listed veins is not possible because the patient is aged or has
other catheters or the like occupying the preferred locations,
alternative locations are within the scope of the invention. Use of
an insertion diameter of 8 French or less (3 F/mm) is generally
preferable, but larger catheters are within the anticipated scope
of the invention. Use of any of the cooling catheters described
above is anticipated, as would be the use of any acceptable
intravenous cooling catheter.
[0089] In step two, the catheter is advanced until the heat
exchange region is in the blood stream flowing to the heart. This
catheter placement is easily accomplished by those of skill in the
art. It may be advanced using a guide wire, without a guide wire,
using a guide catheter, or without a guiding catheter. It may be
advanced using other well-known techniques as appropriate for the
situation and the structure of the catheter, for example using bare
wire or rapid exchange technique if applicable. It may be advanced
from the femoral vein into the IVC, from an internal jugular
insertion into the internal jugular vein into the SVC or the IVC,
or if appropriate, even into the heart itself from either femoral
or internal jugular insertion. Any location for the insertion and
placement of the catheter that results in cooling of the blood
directed to the heart is within the anticipated scope of this
disclosure.
[0090] In step three, the heat exchange region is cooled below the
temperature of the blood. The heat exchange region may be cooled to
about 0.degree. C., although it should not be cooled much below
that temperature. The blood is largely water and is generally not
damaged by contact with a surface that is as cold as 0.degree. C.
for the length of time that the blood is in contact with the heat
exchange region, but with a surface much colder than that, blood in
contact with the heat exchange region would freeze, possibly
damaging the blood and decreasing the effectiveness of heat
exchange. However, cooling below that temperature might be
acceptable if an acceptable, safe and efficient method of cooling
were employed, as long as it resulted in the cooling of the heart
by means of cooling of the blood directed to the heart to reduce
infarct suffered as a result of an ischemic event. The method
described in greatest detail above of reducing the temperature of
the heat exchange region was circulating cold saline through a
balloon or hollow metallic element, or multiple heat exchange
elements, to exchange heat with the blood through the surface of
the heat exchange element, but other acceptable means of cooling
the heat exchange region may be employed in practicing this
invention.
[0091] The fourth step of the invention involves maintaining the
exchanging of heat for a sufficient length of time to reduce the
temperature of the heart. In the examples shown, about 240 watts of
heat were being removed from the blood in the IVC to lower the
temperature of the heart from 38.degree. C. to about 33.degree. C.
in about 55 minutes. Depending on the desired level of hypothermia,
the amount of blood flowing past the catheter, the number of watts
of heat being removed from the blood by the heat exchange region,
and similar variables, that rate of cooling may well be different
and still be within the scope of this invention. It is generally
the case that the cardiac temperature will be lowered to 35.degree.
C. or less to enjoy the benefits of mild hypothermia to reduce
infarct, but depending on the individual situation, this may vary
somewhat and still fall within the scope of this invention.
[0092] The application of hypothermia may be before the ischemic
event, if an ischemic event is anticipated as is the case in
surgery when it is known that the heart will be stopped for some
period of time, or during balloon angioplasty when it is known that
areas of the heart downstream of the balloon will be deprived of
blood for some period of time. The hypothermia may be applied
during the ischemia, as when it is applied during the two
situations described above, whether or not it was applied before
the ischemic event, or when it is applied to a heart attack victim
when that victim presents. It may be applied after the ischemic
event has occurred, as when it is applied to a heart attack victim
soon after the ischemic event has occurred but after the ischemia
has resolved and reperfusion has occurred. In all these cases and
in combinations thereof, the application of mild hypothermia will
generally be beneficial to prevent infarct from resulting from the
ischemic event.
[0093] Step 5 involves controlling the heat exchange region in
response to heart temperature. This generally involves monitoring a
temperature such as rectal, tympanic, esophageal, cardiac or other
temperature that may be used to determine the temperature of the
heart, and controlling the heat exchange region in response to that
measurement. The control of the heat exchange region may be in many
forms. One form described in detail above was the control of the
temperature of heat exchange fluid being circulated through a heat
exchange balloon that comprised the heat exchange region. This
could be done, for example, by controlling the temperature of an
external heat exchanger that was in contact with a bag of saline,
which saline was being circulated through the heat exchange
balloon. However, if the heart temperature is determined by other
factors, such as the length of time of cooling, the amount of heat
transfer, or other physiological measurements, the control may be
exercised based on these features.
[0094] The specific activities that may constitute control are
many. Cooling may be stopped and heat added to the blood after the
heart has reached a certain target temperature. Alternatively, the
heat exchange region may be removed, or the heat exchange region
may be returned to normothermia. In a more elegant type of control,
a target temperature may be pre-selected and the amount of heat
added or removed from the blood may be adjusted so that the cardiac
temperature achieves the target temperature and stays at the target
temperature for some pre-selected length of time, and then may warm
or cool toward a second pre-selected temperature that may be
normothermia, or the like. The nature of the control in response to
the temperature of the heart may vary greatly and still be within
the scope of this invention.
[0095] Step six, optional but sometimes a step practiced in the
method, is to add heat to the hypothermic heart.
[0096] Although several illustrative examples of means for
practicing the invention are described above, these examples are by
no means exhaustive of all possible means for practicing the
invention. The scope of the invention should therefore be
determined with reference to the appended claims, along with the
full range of equivalents to which those clams are entitled.
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