U.S. patent application number 13/294140 was filed with the patent office on 2012-03-08 for intravascular device for neuromodulation.
Invention is credited to Lynn Elliott, Daniel W. Fifer, Colleen Stack N'diaye, Richard S. Stack, Michael S. Williams.
Application Number | 20120059431 13/294140 |
Document ID | / |
Family ID | 38179674 |
Filed Date | 2012-03-08 |
United States Patent
Application |
20120059431 |
Kind Code |
A1 |
Williams; Michael S. ; et
al. |
March 8, 2012 |
Intravascular Device for Neuromodulation
Abstract
The present disclosure describes intravascular systems that may
be used for a variety of functions. The elements of the disclosed
systems include at least one device body implanted within the
vasculature. Electrodes on a lead and/or on the device body itself
are used to direct electrical energy to neurological targets. These
systems may additionally include one or more fluid reservoirs
housing drugs or other agents to be delivered to tissue.
Inventors: |
Williams; Michael S.; (Santa
Rosa, CA) ; Stack; Richard S.; (Chapel Hill, NC)
; Elliott; Lynn; (Maple Grove, CA) ; N'diaye;
Colleen Stack; (Hillsborough, NC) ; Fifer; Daniel
W.; (Windsor, CA) |
Family ID: |
38179674 |
Appl. No.: |
13/294140 |
Filed: |
November 10, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11702000 |
Feb 2, 2007 |
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13294140 |
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60765420 |
Feb 3, 2006 |
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Current U.S.
Class: |
607/5 ; 607/61;
607/62; 607/72; 607/9 |
Current CPC
Class: |
A61N 1/0531 20130101;
A61N 1/05 20130101; A61N 1/0551 20130101; A61N 1/0534 20130101;
A61N 1/3605 20130101; A61N 2001/0585 20130101; A61M 2205/3523
20130101; A61N 1/36082 20130101; A61M 5/14276 20130101; A61N 1/3627
20130101; A61N 1/0529 20130101; A61N 1/36114 20130101; A61N 1/36117
20130101; A61N 1/36071 20130101; A61N 1/057 20130101 |
Class at
Publication: |
607/5 ; 607/72;
607/9; 607/61; 607/62 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/372 20060101 A61N001/372; A61N 1/378 20060101
A61N001/378; A61N 1/39 20060101 A61N001/39; A61N 1/362 20060101
A61N001/362 |
Claims
1. A method of electrically modulating a nervous system target,
comprising the steps of: introducing a neuromodulation implant into
the vasculature of a patient, the neuromodulation implant including
a device body and a pulse generator within the device body;
positioning at least one electrode within a superior vena cava of
the patient, the electrode in communication with the device body,
chronically retaining the neuromodulation implant within the
vasculature; and with the electrode in the superior vena cava,
stimulating the nervous system target using the electrode.
2. The method of claim 1, wherein chronically retaining the
neuromodulation implant retains the electrode in the superior vena
cava.
3. The method of claim 2, wherein, when the neuromodulation implant
is chronically retained, the device body is disposed in an inferior
vena cava and the electrode is disposed in the superior vena
cava.
4. The method according to claim 1, wherein the electrode is on a
lead, and wherein the method further includes passing the lead and
electrode into the superior vena cava to position the
electrode.
5. The method according to claim 4, further including anchoring the
lead within the superior vena cava.
6. The method according to claim 1, wherein the nervous system
target includes a parasympathetic nervous system target.
7. The method according to claim 1, wherein the nervous system
target includes a sympathetic nervous system target.
8. The method according to according to claim 1, wherein
stimulating the nervous system target includes stimulating a
cardiac parasympathetic nerve target to treat atrial
fibrillation.
9. The method according to claim 1, wherein stimulating the nervous
system target includes stimulating the vagus nerve to treat heart
failure.
10. The method of claim 1, wherein retaining the implant includes
expanding an anchor into contact within the wall of the superior
vena cava, the anchor retaining the implant.
11. The method according to claim 1, wherein the neuromodulation
implant includes a power source, and wherein the method further
includes wirelessly recharging the power source using an external
charging device.
12. The method according to claim 11, wherein the external charging
device recharges the power source using inductive coupling.
13. The method according to claim 11, wherein the external charging
device recharges the power source using an optical energy source
impinging radiant energy through the body to a photovoltaic cell
electrically connected to the power source.
14. The method according to claim 11, wherein the external charging
device recharges the power source using a mechanical energy source
impinging vibrational energy through the body to a piezoelectric
element electrically connected to the power source.
15. A neuromodulation system comprising: a neuromodulation implant
including an intravascular pulse generator; an anchor engageable
with a wall of a superior vena cava to anchor the neuromodulation
implant within the vasculature; and at least one electrode carried
by the anchor, wherein engagement of the blood vessel wall by the
anchor positions the electrode in contact the superior vena cava
wall proximate to a nervous system target.
16. The system according to claim 15, further including a lead
extending between the pulse generator and the anchor, wherein the
anchor is on the lead.
17. The system according to claim 16, including a plurality of
electrodes on the anchor.
18. The system according to claim 15, wherein the anchor is a
member radially expandable into contact with a blood vessel wall,
wherein the electrode is on the radially expandable member.
19. The system according to claim 18, further including a plurality
of electrically isolated electrodes on the member.
20. The system according to claim 15, wherein the neurostimulation
implant is proportioned such that the pulse generator is disposed
in an inferior vena cava when the anchor is engaged with the
superior vena cava.
21. The system according to claim 15, wherein the system includes a
sensor device positioned to detect a body condition, the implant
configured to deliver one or more neuromodulation pulses at the
electrode in response to feedback from the sensor device.
22. The system according to claim 21, wherein the sensor device is
on the implant.
23. The system according to claim 22, wherein the sensor device is
coupled to the implant and positionable at a location in the body
remote from the anchoring location.
24. The system according to claim 21, wherein the sensor device is
in wireless communication with the implant.
25. The system according to claim 21, wherein the sensor device is
an extracorporeal sensor.
26. The system according to claim 21, wherein the sensor is
configured for implantation with the body of the patient.
27. The system of claim 15, wherein the implant includes a
rechargeable power source, and wherein the system further includes
an external charging device positionable to inductively couple
energy to the rechargeable power source.
28. The system according to claim 15, further including a second
anchor expandable to anchor a portion of the implant within a
second blood vessel.
29. The system according to claim 28, wherein the second blood
vessel is the inferior vena cava.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of co-pending U.S. Ser.
No. 11/702,000, filed Feb. 2, 2007, which claims the benefit of
U.S. Provisional Application No. 60/765,420, filed Feb. 3,
2006.
FIELD OF THE INVENTION
[0002] The present invention generally relates to implantable
devices and systems, and associated methods for delivering therapy
to the neurological system.
BACKGROUND OF THE INVENTION
[0003] "Neuromodulation" is the therapeutic alteration of activity
in the central, peripheral or autonomic nervous systems,
electrically and/or pharmacologically, by means of implanted
devices. Implantable medical devices are used to deliver
neuromodulation therapy to patients to treat a variety of symptoms
or conditions. For example, some the implantable medical devices
deliver neurostimulation therapy in the form of electrical pulses.
For some conditions, electrical stimulation is performed in
combination with drug therapy using implantable drug pumps that
deliver drugs to the nerves undergoing neurostimulation.
[0004] U.S. Publication No. US2005/0043765 ("765 publication")
Intravascular Electrophysiological System and Methods (filed Jun.
4, 2004 and commonly owned with the present application), which is
incorporated herein by reference, describes intravascular systems
that may be used to deliver electrical energy to the heart such as
for defibrillation, pacing, and/or cardioversion of the heart.
[0005] Such systems include at least one housing containing the
necessary pulse generator and associated electronics, circuitry and
related components, and they optionally include at least one lead
carrying some or all of the electrodes needed to deliver the
electrical energy to the body. Some or all of these components are
positioned within the vasculature, such as in the superior vena
cava ("SVC"), the inferior vena cava ("IVC"), the left or right
subclavian vein ("LSV" or "RSV"), coronary sinus and/or within
other vessels in the venous or arterial system. For some of the
implant components (such as the housing and/or lead), anchoring
devices may be needed to retain the implant within the
vasculature.
[0006] U.S. Publication No. 2005/0234431 ("431 publication"),
Intravascular Delivery System for Therapeutic Agents (filed Feb.
10, 2005 and commonly owned with the present application), which is
incorporated herein by reference, describes systems for
intravascular drug delivery system. Certain ones of the embodiments
of the described systems include a reservoir implantable within a
blood vessel, an intravascular pump fluidly coupled to the
reservoir and an anchor 16 expandable into contact with a wall of
the blood. vessel to retain the system within the vasculature.
Delivery conduits 108 (FIG. 11 of the '43.1 publication) may extend
from the reservoir and are positionable at select locations within
the vasculature for target drug delivery to select organs or
tissues. Throughout this disclosure, the terms "drugs" and "agent"
will be used to refer to any substances to be delivered into the
body for any purpose including, but not limited to, prophylactic or
therapeutic purposes. In some cases, such substances might also be
biologic, such as vector-directed or mediated gene therapy,
microspheres containing releasable agents, or stem cells modified
to express certain proteins or other therapeutic or diagnostic
compounds.
[0007] As disclosed in each of the above-referenced applications as
well as U.S. Publication No. 2006/0217779 Flexible Hermetic
Enclosure for Implantable Medical Devices (filed Mar. 24, 2005 and
commonly owned with the present application), which is incorporated
herein by reference, these types of implantable devices may be long
and narrow for implantation into the vascular, and in some cases
can be approximately 10-60 cm in length. Such devices are
preferably sufficiently flexible to move through the vasculature
yet sufficiently rigid to protect the internal components. Certain
embodiments described in the above-referenced patent applications
build flexibility into the elongate implants by assembling them
using a plurality of segments, with each segment defining interior
space for components to be housed within it. Each segment may be
separately enclosed by its own enclosure, with several such
enclosures coupled together to form the implant. The enclosures are
interconnected at articulations formed using silicone rubber filler
or mechanical bellows.
[0008] It is believed that intravascular devices of the type
described in the referenced applications may be suitable for use as
neuromodulation devices to delivery electrical and/or
pharmaceutical therapy to the nervous system.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIGS. 1A-1C are block diagrams showing three exemplary
embodiments of neurostimulation systems.
[0010] FIGS. 2A and 2B are plan views showing implantable
neurostimulation components and associated implant tools.
[0011] FIG. 3 is a plan view of an implant showing flexible
interconnects between portions of the implant.
[0012] FIG. 4A is a perspective view showing an anchor.
[0013] FIG. 4B is a cross-section view taken along the plane
designated 4B-4B in FIG. 4A.
[0014] FIG. 4C is a side elevation view of the anchor of FIG. 4A
mounted on an implant device and compressed by a sheath.
[0015] FIG. 4D schematically illustrates use of the anchor of FIG.
4C to support the implant device within the inferior vena cava.
[0016] FIGS. 5-13 are schematic illustrations showing the heart and
associated vasculature, and illustrating placement of
neurostimulation devices within the body.
DETAILED DESCRIPTION
[0017] Generally speaking, the present disclosure describes
intravascular systems that may be used for a variety of functions.
In general, the elements of the systems described below include at
least one device body and typically, but optionally, at least one
lead coupled to the body. The device body (which may include a
number of body segments coupled to one another) is ideally
positioned fully within the vasculature of the patient. Electrodes
on the lead and/or on the device body itself are used to direct
monopolar or bipolar electrical energy to neurological tissue or
associated structures. These systems may additionally include one
or more fluid reservoirs housing drugs or other agents to be
delivered to tissue. If drug delivery in combination with
electrical therapy is contemplated, the lead(s) may include fluid
conduits positioned to direct drugs/agents towards the area of the
nervous system that is to be stimulated. Combined delivery of
electrical stimulation and drugs/agents might also be used to
activate a drug, or to treat a tissue to create an electroporation
of a cell to make it more receptive to the administered drug, or to
release drugs from drug-containing microspheres having walls that
burst or increase in porosity when subjected to electrical
stimulation. In other embodiments, neurostimulation is provided
using agents (e.g. local application of neurotransmitter,
neurotransmitter receptor agonists, neurotransmitter receptor
antagonists, or other agents to nervous system target) with or
without the use of electrical pulses. Electrical stimulation and/or
drug delivery can also be directed to other neurological or
non-neurological targets (including organs and/or associated
systems) to simulate the release or inhibition of naturally
produced agents such as adrenaline or insulin.
[0018] Separate fluid delivery leads may also or alternatively be
used to direct drugs/agents to an organ (e.g. kidneys, heart) or to
other sites remote from the neural tissue undergoing stimulation.
One or more anchors/retention devices may facilitate retention of
the device body and/or leads or other elements within the
vasculature.
[0019] FIGS. 1A through 1C are block diagrams illustrating three
exemplary intravascular neurostimulation systems. In the first
system 100 shown in FIG. 1A, neurostimulation implant device 12
houses a power source 11 which may include a battery and a power
generation circuit to produce operating powerstimulation. Device 12
also includes a pulse generator 13 for generating stimulation
pulses for transmission to the patient via electrodes 25 on leads
14 or directly on the body of the implantable device 12. A
processor 30 may be included for controlling operation of the
device 12.
[0020] Various stimulation parameters may be used depending upon
the target structure and therapeutic application. In general, pulse
sequences may use one or all of the following parameters:
amplitudes within the range of approximately 1 to 50 mAmp, pulse
widths of 1 to 1000 .mu.s, burst rates of 1 to 500 Hz, and
programmable duty cycles of 1% to 100%. For some applications,
continuous electrical stimulation may be used, or pulse sequences
having pulses of different parameters might be employed (e.g. for
ventricular rate control in atrial fibrillation, the system might
deliver pacing pulses and high-frequency neurostimulation during
the atrial refractory period to prevent atrial excitation). The
parameters may vary (e.g. ramp up or down) within a pulse sequence,
or remain constant. Charge balancing of pulses is appropriate for
preventing corrosion/electrolysis of the leads within the tissue.
This is generally accomplished using wave forms having biphasic
morphology or timing the capacitor recharge cycles such that there
is no net imbalance of charge following stimulation.
[0021] The functionality of the system 100 may be enhanced using
one or a combination of several additional features. For example,
the system 100 may include a battery that is rechargeable. An
external charger 32 positioned outside the patient inductively
couples to a charging circuit 33 within the device 12 to recharge
the battery. The external charger 32 includes a charging coil
energizable to create an electromagnetic field that in turn induces
current in a corresponding coil within the charging circuit 33. The
coil may be mounted to a waist pack, wearable
skin-contacting/adhering patch, purse, backpack, or wheelchair
cushion so that it can be carried by the patient in sufficient
proximity to the charging circuit 33. Alternatively, the coil may
be positioned within a pad positionable on a patient's mattress,
allowing for charging of the battery while the patient rests.
[0022] In other embodiments, external charger 32 might be replaced
with an external inductive power supply for transcutaneously
powering the pulse generator whenever stimulation therapy is to
occur, thereby obviating the need for the battery. Energy
harvesting techniques may be used by which energy generated by the
body may be converted for use in charging the battery and/or
operating the system. Piezoelectric elements mounted at various
locations in the body might, for example, be used to convert motion
of the heart, pulsing blood vessels, limbs, or other structures to
electrical energy.
[0023] The system 100 may also include an external programmer 34
that communicates with a telemetry interlace 36 within the
implantable device 12 using radio frequency encoded signals or
other telemetric methods. Telemetry systems permitting external
devices to communicate with implanted medical devices are known in
the art. See, for example, U.S. Pat. Nos. 6,824,561, 5,312,453 and
5,127,404. A user may use the programmer 34 to configure the device
12 (e.g. to set dosing schedules, to set the thresholds above/below
which stimulation will be given, to set stimulation parameters), to
review the history of therapy given by the implant, to test the
implant, to allow the patient to direct release of analgesics for
pain control, etc. Where multiple electrodes are employed, the
programmer 34 may be used to identify the most optimal electrode
pair for stimulating the target structure as discussed in greater
detail below.
[0024] Sensors 38 can be positioned for detecting certain
conditions of the patient and for transmitting signals indicative
of the sensed conditions. Signals corresponding to the sensed
conditions may be used to trigger the delivery of therapy (see
"Control Mechanisms" below) and/or sensor output may be stored
within the device for subsequent retrieval using external
programmer 34.
[0025] Sensors 38 may be located on the device body 12 or the leads
14, or coupled to the device body 12 or leads 14 using cables. For
some applications, sensors 38a may be separate implantable or
extracorporeal components having communication features allowing
them to communicate with the implant 12 via the telemetry interface
36 and/or with external. programmer 34.
[0026] FIG. 1B shows a second system 10a that differs from the
system of FIG. 1A in the incorporation of a drug delivery reservoir
and pump features 40 allowing administration of drugs from the
reservoir to drug leads 14a (e.g. microtubules) extending from the
device. These drug delivery features may be enclosed within the
same housing occupied by the other components, or the drug delivery
components and neurostimulation components may be divided into two
or more separate housings electronically coupled to one another. It
should be noted that the FIG. 1A embodiment may be altered to
provide only drug delivery, such as for neurostimulation using
agents only (e.g. neurotransmitter, neurotransmitter receptor
agonists, neurotransmitter receptor antagonists, analgesics),
without the use of electrical stimulation.
[0027] The system 100b of FIG. 1C is similar to the system of FIG.
1B, but differs in that the neurostimulation features and drug
delivery features are contained within physically separate
housings. According to this embodiment, the drug reservoir and pump
features 40 are enclosed within a container 42 having its own power
source 44 as well as communication features 46 for receiving
signals wirelessly transmitted by the telemetry interface 36 in the
device 12b. With this arrangement operation of the drug delivery
pump can be governed wirelessly by the processor housed in the
device 12b in a master-slave type configuration. In variations on
this embodiment, the arrangement of components might be reversed
such that the device 12b includes the slave components remotely
controlled by a processor within the container 42. In another
variation, both the neurostimulation components of the device 12b
and the drug delivery components of the container 42 are wirelessly
controlled using a third device implanted within the body (e.g. in
the vasculature or in a subcutaneous location) or positioned
external to the body. Other systems might employ multiple
neurostimulators and/or drug delivery devices independently
controlled or controlled using a common master device either
directly or wirelessly. In yet another variation using separate
drug delivery and neurostimulation implants, one or the other (or
both) of the implants may be positionable outside the
vasculature.
System Components
[0028] FIGS. 2A and 2B illustrate exemplary neuromodulation devices
and associated components for use in implantation and anchoring of
the devices.
[0029] The elements of the FIG. 2A system include elongate device
body 12, lead 14, retention device 16, sleeve 17, positioning
mandrel 18 and introducer sheath 19. It should be understood that
certain of these elements may be eliminated, or others added. to
the system, without departing from the spirit and scope of the
invention.
[0030] As discussed in connection with FIGS. 1A-1C, device 12
houses components known in the art to be necessary to carry out the
system functions. For example, device 12 may include one or more
pulse generators, including associated batteries, capacitors,
microprocessors. and/or circuitry for generating electrical
stimulation pulses and/or drug reservoirs and associated pumps
associated with drug delivery. The '431 publication provides
examples of features drug reservoirs, pumps or other drug delivery
mechanisms, and other features that may be included in a
neuromodulation device having drug delivery capabilities. As
discussed in greater detail in the section entitled "Control
Mechanisms", device 12 may include sensors and detection circuitry
for detecting the onset of neurological episodes (e.g. seizures) or
other conditions within the body, and/or it may be equipped to
directly or wirelessly receive feedback signals from sensors
positioned elsewhere inside or outside the body. The specific
sensors and other components to be provided in the device will
depend upon the application for the device.
[0031] The device 12 is proportioned to be passed into the
vasculature and to be retained within the patient's vasculature.
Suitable sites for the device 12 may include, but are not limited
to, the venous system using access through the right or left
femoral vein or the subclavian or brachiocephalic veins, or the
arterial system using access through one of the femoral arteries.
Specific vessels within which the device can be retained include
the superior vena cava, inferior vena cava, jugular vein,
subclavian vein, axillary vein, and the iliac vein, amongst
others.
[0032] If the device is to be positioned in an essential blood
vessel, it is desirable to minimize obstruction to blood flow
presented by the device. In that case, the transverse
cross-sectional area of the implant is preferably <50% of that
of the vessel. Thus, the housing of device 12 preferably has a
streamlined maximum cross sectional diameter which may be in the
range of 1-15 mm or less, with a most preferred maximum
cross-sectional diameter of 1-8 mm or less. The cross-sectional
area of the device in the transverse direction (i.e. transecting
the longitudinal axis) should be as small as possible while still
accommodating the required components. This area may be within the
range of 5-175 mm.sup.2. Other acceptable ranges of cross-sectional
areas are those within the ranges of approximately 79 mm.sup.2 or
less approximately 40 mm.sup.2 or less, or 12.5-40 mm.sup.2
[0033] The cross-section of the device (transecting the
longitudinal axis) may have a circular cross-section, although
other cross-sections including crescent, flattened, or elliptical
cross-sections may also be used. It is highly desirable to provide
the device with a smooth continuous contour so as to avoid voids or
recesses that could encourage thrombus formation on the device.
[0034] Depending on the components to be included in the device 12,
the device may utilize a single- or multiple-compartment housing
having a length in the range of 1-100 cm.
[0035] A proximal portion of the device includes a connector 25 for
receiving the distal end of positioning mandrel 18, which may be
used to steer the device 12 (by pushing, pulling and/or torquing)
through the patient's vasculature to a target location as described
in detail in the above-referenced applications. The connector 25
may take the form of a threaded bore for receiving a threaded screw
member at the distal end of the mandrel 18, or it may have any
other type of configuration for detachably engaging the distal end
of the mandrel. Mandrel 18 can also function as an explant tool
used to engage the device 12 and withdraw it from the body.
[0036] Mandrel 18 may serve purely mechanical purposes, or it may
also be a "smart mandrel" that provides electrical and/or fluid
connections. Such connections can be used to couple the device (via
an instrument cable) for electrical, electronic, and/or fluid
communication between the device and instrumentation located
outside the body. This communication may be used for several
purposes, including device testing, initiation and/or programming
during implantation, and/or recharging of the device battery. If
the device is to be used for drug delivery, the mandrel may be used
for re-filling a reservoir in the device with drugs/agents that may
be deliverable by the device to a patient.
[0037] The position of the lead 14 relative to the device is
preferably selected to orient the lead in the direction of the
vessels (relative to the vessel in which the device body 12 is
positioned) that will receive the lead 14. In the FIG. 2A example,
lead 14 is attachable to the inferior end of device 12 (the lead 14
may alternatively be integrally connected to the device). Lead 14
includes one or more electrodes 26 configured to pass electrical
energy through wall of the surrounding vessel into the targeted
neurological structure or directly into the neurological
tissue.
[0038] Including a number of separate electrodes (e.g. a
longitudinal array of electrodes, which may number from 2-16 or
more, or a two- or three-dimensional electrode grid such as a
4.times.4 grid) per lead can provide a number of advantages. For
example, where many electrodes are provided, the system can
electronically change which of electrodes in the array serves as
the anode and which serves as the cathode, such that the effective
site of stimulation can be moved without physical repositioning of
the lead. The precise location of a neurological target may not
always be known. With this capability, the system can sample
various electrode pairs to evaluate which combination of electrodes
will yield the most optimal response to stimulus. It is
contemplated that such electronic manipulation of the electrodes
can be done real time and continuously to provide for either
isolated point stimulation using closely spaced electrodes or broad
tissue capture using more widely separated electrodes. It is also
contemplated that the movement of the stimulation site might be
useful in managing/reducing damage or sensitization of local tissue
to stimulation.
[0039] Another advantage to the use of multiple electrodes or
electrode pairs is that it allows for selective stimulation by
means of using various electrode pairs to interfere with the
propagation of electrical impulses in one direction while
simultaneously (or sequentially) using separate electrode pairs to
induce electrical stimulus propagation in the opposite direction
along nerve fibers.
[0040] Examples of electrodes that might be used include surface
electrodes or tip electrodes. In other embodiments, electrodes that
engage the walls of the surrounding vessel might be used. For
example, an electrode may be an expandable electrode similar in
structure to the anchor 16, or the anchor 16 may be provided with
multiple electrodes formed on or mounted to it. This type of
embodiment might take the form of a polymeric stent-like grid with
an array electrodes, each insulated from the other, throughout the
grid structure. This arrangement allows stimulation to be delivered
over a greater surface area (e.g. around the inner surface of a
vessel wall) and might be particularly useful where the general
location of the neurological tissue is known but the precise
location is difficult to determine. As another example, the leads
may include tip electrodes having penetrating elements that engage
the vessel wall. For some applications, leads having
electrode-bearing needle tips may be used to allow the electrode(s)
to be passed through the vessel wall into the nerve or nerve bundle
or to a superficial position from which the lead can be connected
surgically to a remote target or a separate remote electrode. The
needle tips may include features (e.g. barbs, helices, expandable
anchors) that allow them to engage the surrounding neurological
tissue. The leads might also be equipped to sense electrical
activity of the target structures, such as for detecting the onset
of a seizure. In such embodiment, activity sensed by the sensing
electrode(s) may be used by the device electronics to trigger
delivery of a neurostimulation pulse or one or more pulse
sequences.
[0041] Additional leads may be provided if desired such that two or
more leads may be positioned to stimulate neurological tissue at
different locations. Where multiple leads are used, stimulation
delivered by each lead may be simultaneous or sequential, or
activation of each lead for delivery of therapy may be independent
of activation of the other lead(s), with energization of each lead
dependent on some sensed condition within the body. The
neurostimulation leads may be provided alone or in combination with
one or more drug delivery leads (e.g. conduits such as
microtubules) positionable to deliver drugs or other agents to
organs or other body tissues. Control of drug delivery may be timed
to be contemporaneous with, sequential to, or independent of
electrical stimulation.
[0042] Electrical stimulation leads 14 may be conventional
neurostimulation leads, although alternative lead configurations
may be desirable if warranted by the desired placement of the
device 12 and lead within the body. Leads of the type used for
defibrillation and/or pacing may be more suitable for some
applications given their suitability for use in the vasculature.
The physician will preferably want to select a location for the
device 12 within a chosen vessel (e.g. the inferior or superior
vena cava or aorta) that will prevent the device from blocking
significant peripheral vessels extending from that vessel. An
optimal lead will preferably give the physician implanting the
device flexibility to position the device at an appropriate
location in the chosen vessel without concern that the leads
extending from the device will not reach their intended location,
but will avoid leaving excess lead length bunched within the
vasculature. Thus, for some patients it may be necessary to use a
lead that is slightly shorter than defibrillation/pacing leads, or
the lead may have a length that is variable/extendable using
various techniques such as those described in the '765
publication.
[0043] The leads 14 and device 12 may include coatings or coverings
made of polymers such as polyurethane. The leads and device may
also include non-thrombogenic and/or non-proliferative surfaces or
coatings as also described in the referenced applications. For
example, the leads and device body may include a coating that is
anti-thrombogenic (e.g. perfluorocarbon coatings applied using
supercritical carbon dioxide) so as to prevent thrombus formation
on the lead. It is also beneficial for the coating to have
anti-proliferative properties so as to minimize endothelialisation
or cellular ingrowth, since minimizing growth into or onto the
lead/device will help minimize vascular trauma when the device
and/or lead is explanted. The coating may thus also be one which
elutes anti-thrombogenic compositions (e.g. heparin sulfate) and/or
compositions that inhibit cellular in-growth and/or
immunosuppressive agents.
[0044] It should also be noted that the lead may be attachable to
the device 12 in situ or prior to implantation, or it may be
permanently attached to the device, or it may be integral with the
device as an elongate extension of the device itself. Thus it
should be appreciated that in this disclosure the term "lead" is
used to mean an element that includes conductors and electrodes
and/or fluid lead conduits and that thus may be positioned somewhat
remotely from the circuitry that energizes the electrodes or the
reservoir that supplies agents to the fluid conduits. Thus, leads
may include elements that are simply extensions or tapers of the
device 12 itself (such as the superior portion of the device 12) as
well as more conventional leads.
[0045] A second embodiment of a device 12 and associated implant
components is shown in FIG. 1B and differs from the FIG. 1A
embodiment primarily in that its lead 14 is attachable (or
integrally attached) to the superior end of device 12. This
arrangement might be suitable for use in delivering stimulus to
features positioned superiorly relative to the device 12 position
within the vasculature.
[0046] As further discussed in the '765 application, each of the
leads may include a guidewire lumen to aid in implantation of the
lead. Referring to FIG. 1, the system may include guidewires 21 for
use in implanting the leads. If multi-site stimulation and/or drug
delivery is desired, two or more leads may be used. Devices for
these applications may include both superior and inferior leads,
multiple leads extending from the inferior and/or superior end,
and/or leads extending laterally from the device body. Using
separate neurostimulation and drug delivery implants as discussed
in connection with FIG. 1C gives the user flexibility to deliver
different forms of therapy to different regions of the body. For
example, a system might include a neurostimulation device be
positioned on the venous side of the cardiovascular system and a
drug delivery system positioned within the arterial system.
[0047] As mentioned, where the device body 12 is particularly long,
the body should be sufficiently flexible to move through the
vasculature while being sufficiently rigid to protect the internal
components. FIG. 2 shows one example of a flexible device body 12c
which employs one or more rigid enclosures 50, or "containers,"
used to contain electronic components to be implanted inside the
vasculature of a patient. The containers 50 house components known
in the art to be necessary to carry out the system functions. For
example, the containers within an implant device can collectively
include one or more pulse generators, including associated
batteries, capacitors, microprocessors, and/or circuitry for
generating electrical pulses for neurostimulation, and or fluid
reservoirs and associated pumps for drug delivery. The applications
referred above provide additional information of these types of
components, as well as suitable arrangements of these components
within the device body.
[0048] Any appropriate number of the containers 50 can be
mechanically connected using interconnecting bellows 52 to form a
flexible device. For many devices, this might include a string of
at least three containers. The sequence of devices and linking
bellows can be repeated as necessary to make a device of an
appropriate length. For example, as shown in FIG. 2, a device 12c
may have several containers 50 connected using multiple bellows 52
as needed to accommodate the components needed for performance of
the device. Additional features of the containers and
interconnection mechanisms are disclosed in the above-referenced
applications.
[0049] The neurostimulation implant device 12 is designed to be
retained entirely within the vasculature. Retention within the
vasculature can be achieved in one of several ways. For example, if
positioned in a non-essential vessel, the device can be retained
through frictional contact with the vessel wall. The flow of blood
within a vessel can also be relied upon to retain the device in a
vessel, preventing the device from migrating upstream while the
physical structure of the vessel prevents downstream migration. In
other embodiments, anchoring the lead 14 in a blood vessel (i.e.
the same or a different blood vessel within which the device 12 is
positioned) or outside the vasculature (e.g. through a vessel wall)
will serve to retain the device which is coupled to the lead. In
other embodiments including those illustrated in FIGS. 5 through
13, an anchor in contact with the device 12 may be used to retain
the device within a blood vessel.
[0050] FIGS. 4A though 4D illustrate one example of an anchor 16 of
the type that may be used to anchor the device 12 in the
vasculature. The anchor 16 is beneficial in that it is implanted
integrally with the device, and thus does not require a separate
implantation step.
[0051] Referring to FIG. 4A, anchor 16 includes structural features
that allow the anchor to radially engage a vessel wall. For
example, a band, sleeve, mesh or other framework formed of one or
more shape memory (e.g. nickel titanium alloy, nitinol, thermally
activated shape-memory material, or shape memory polymer) elements
or stainless steel, Elgiloy, or MP35N elements may be used. The
anchor may include anti-proliferative and anti-thrombogenic
coatings, although in this embodiment the anchor structure 16 or
adapted to promote tissue ingrowth to as to enhance anchor
stability within the vessel. The anchor may also have drug delivery
capability via a coating matrix impregnated with one or more
pharmaceutical agents.
[0052] FIG. 4B shows one anchor 16 attached to a device 12,
although naturally one, two or more such anchors may alternatively
be used. In one embodiment, anchor 16 is attached to the implant 12
by a c-shaped collar 54, or other suitable connection. The implant
12 may include a recessed portion 56 that allows the exterior of
the anchor to sit flush with the exterior of the implant 12 when
the anchor is its compressed position. The recessed portion should
have smooth contours in order to discourage thrombus formation on
the device.
[0053] The anchor 16 and device 12 may be detachably connected to
the recessed portion using methods that allow the anchor 16 and the
implant 12 to be separated in situ, for permanent or temporary
removal of the implant 12. A detachable connection between the
anchor 16 and implant 12 may utilize a snap fit between the collar
54 and implant 12. As shown in FIG. 4B, both the collar and the
recessed. portion 56 of the implant may include an elliptical
cross-section. if it becomes necessary to remove the medical
implant from the patient's body, the medical implant may be torqued
about its longitudinal axis, causing the body of the implant to cam
the edges of the collar to a slightly opened position, thereby
allowing the implant to be passed between the edges of the collar.
Other features of the anchor 16, as well as examples of alternative
designs, are discussed in the '765 publication.
[0054] Referring to FIG. 4C, a retractable sheath 17 may be
slidably positioned over the anchor 16 and implant so as to retain
the anchor in its compressed position. Retraction of the sheath as
indicated in FIG. 4D allows the anchor 16 to expand into contact
with the surrounding walls of the vessel, thereby holding the
medical implant in the desired location. Once deployed, the anchor
16 is preferably intimate to the vessel wall, which is distended
slightly, allowing the vessel lumen to remain approximately
continuous despite the presence of the anchor and thus minimizing
turbulence or flow obstruction. In other embodiments, the anchor
may be deployed prior to the device 12, with the device later
attached to the anchor, or it may be deployed after the device 12
with the anchor expandable to sandwich a portion of the device
between the anchor and the vessel wall as disclosed in one
embodiment of the '431 application.
[0055] Control Mechanisms
[0056] The device 12 delivers stimulation according to a control
mechanism appropriate to the particular application for the device.
Exemplary control mechanisms include but are not limited to the
following: (a) open loop control, in which asynchronous stimulation
is delivered without reference to sensor feedback (e.g. stimulation
for pain control): (b) triggered control, in which no stimulation
is delivered until a certain condition is detected and then
asynchronous stimulation is initiated for a prespecified duration
(e.g. stimulation to end an epileptic seizure), and (c) closed loop
control, in which one or more feedback variables are actively
monitored, and in which stimulator output is modified based on this
feedback (e.g. stimulation for control of hypertension by balancing
the reduction in heart rate vs elevation of blood pressure). A
single system (e.g. any of the systems of FIGS. 1A-1C) can be
equipped to use combinations of these control mechanisms for
different forms of therapy to be delivered. For example, in a
single system, closed loop control might be used for
neurostimulation while open loop control is used for dnig
delivery.
[0057] The sensing capabilities of the device will be tailored to
the specific application(s) for use. Possible sensing capabilities
for inclusion in the device include electrical sensing of
physiologic parameters (e.g. heart rate, neurological activity),
biochemical sensors for indicators of a given condition, chemical
sensing of changes in hormone secretion, ionic balances (e.g.
changes in sodium concentrations), or sensing of physical
conditions (e.g. blood pressure, physical activity, volume over
load, etc). The term "patient conditions" will be broadly used to
refer to any type of state or condition that may be detected using
a sensor, including but not limited to the sensors and
states/conditions expressly identified herein.
[0058] The sensors for feedback may be implantable or external, may
be permanent or temporary, and may provide their feedback over
large variations in sampling rate. They may be configured to
transmit signals representing sensed physical/chemical/electrical
parameters over the lead, over separate cabling, or through various
wireless transmission techniques, or they might be imbedded in the
device itself (e.g. a thermistor for core temperature
measurements). Some specific types of sensors will be discussed in
connection with the embodiments of FIGS. 6-13.
[0059] Some applications for the system 10 involve positioning the
electrodes at a location in a vessel such that stimulation pulses
will conduct from the electrodes through the walls of the vessel to
a target nerve located outside the vessel. The system 10 may be
provided with detection features allowing determination of the
point at which the nerve and the vessel cross one another, so that
electrodes nearest the crossing point may be activated for
stimulation. Such features might include use of electrodes to
monitor electrical pukes from the nerve, or to deliver mild
stimulation during implantation so that specific feedback or
patient reaction can be detected when the electrode is close to the
nerve. For example, in the case of phrenic nerve stimulation, such
feedback may take the form of a hiccup triggered in response to
stimulation.
[0060] Exemplary Methods
[0061] For use in performing neuromodulation, a system of the type
described above would be positioned within the arterial, venous, or
coronary vasculature or in the heart, with leads extending through
the vasculature to locations from which electrical stimulus and/or
drugs delivered from the leads will deliver a therapeutic benefit
to the target neurological structures (such as nerves, the spinal
cord, or target regions of brain tissue). For example, for deep
brain stimulation, leads might be positioned to deliver therapy to
deep brain structures such as the subthalamic nucleus and globus
pallidus. In the case of epilepsy, electrodes might be passed
through vessels leading to the region of seizure origin as
determined by prior testing. Alternatively in the case of epilepsy,
brain regions involved in seizures may be affected via stimulation
of afferent fibers of the left vagus nerve by electrode(s) placed
in cervical or thoracic vasculature.
[0062] Where the device is used for electrical or drug stimulation
of nerves, stimulation can be targeted to one or more nerves to
enhance, augment, inhibit or block signaling of efferent, afferent
and/or interneuronal nerve cells, with any combination of these
effects being within the scope of this disclosure. Stimulus can be
directed to a mixed nerve containing both afferent and efferent
nerve cells to produce one effect (e.g. enhance, inhibit or block
signaling) on one type of nerve cell (i.e. the afferent or efferent
nerve cells), and to produce the same or a different effect (e.g.
enhance, inhibit, block, or yield a neutral effect) on the other
type of nerve cell. Alternatively, stimulation can be delivered to
one or more separate afferent nerves, efferent or interneuronal
nerves nerves using the same or different electrodes/fluid conduits
to trigger one of these effects (e.g. enhance signaling, inhibit
signaling, block signaling, or have a neutral or any combination of
the effects).
[0063] FIG. 5 illustrates the device 12 positioned in the IVC with
the lead 14 extending into the peripheral vasculature (shown
schematically) for delivery of therapeutic stimulus to peripheral
nerves. In one application, peripheral nerve stimulation might be
used to aid movement of a limb experiencing paresis due to
peripheral neuropathy. In this application, a sensor is positioned
proximal to the site of the nerve damage. When the sensor detects
nerve signals indicating that the patient is attempting to move the
limb, the electrode is energized to stimulate nerve(s) distal to
the nerve damage. The sensed signal may be detected from the
damaged nerve at a location proximal to the nerve damage, and the
stimulus may be delivered to the damaged nerve ata location distal
to the nerve damage, effectively creating a "bridge" across the
nerve damage. Lead 14 may similarly function to bridge neural
interruptions in a limb that has been reattached. In this example,
the lead 14 extends through a blood vessel beyond the point of
reattachment so that the electrode is positioned to deliver stimuli
to nerve(s) distal to the reattachment. This may require surgical
microconnections of the lead 14 to specific areas within the
cross-section of the proximal and distal nerve segments. In yet
another example, the lead 14 may extend into the prosthetic limb of
an amputee. The signals detected by sensor(s) positioned in the
body are used to trigger delivery of signals to the prosthesis
instructing the prosthesis to move a particular way. In this
embodiment, the prosthesis can be configured to select from a
preprogrammed menu of movement types based on the nature of the
sensed signals.
[0064] Various other applications exist for the use of the
disclosed neurostimulation systems to bridge neural interruptions
at any level within the peripheral or central nervous system.
[0065] It should be mentioned with reference to FIG. 5 that an
electrical or fluid lead positioned in the peripheral vasculature
might also be used to for maintenance of the implant. Thus, a fluid
lead might include a port into which agents may be injected using a
percutaneous syringe in order to refill a fluid reservoir in the
device 12. An electrical lead might include features for
transcutaneous recharging of the battery in the device, such as
inductive charging, optical charging (e.g. using a light source
that transmits light through the skin for impingement onto
photovoltaic cell(s) on the lead) or mechanical charging (e.g.
transmitting mechanical vibrations through the skin to a
piezoelectric element on the lead).
[0066] Additional exemplary methods for use of an intravascular
system of the type disclosed herein are shown in FIGS. 6 through
13.
[0067] FIGS. 6 and 7 illustrate use of an implantable stimulator
for treatment of congestive heart failure ("CHF"). Before the
details of the FIGS. 6 and 7 embodiments are given, some background
on CHF and the body's response to the effects of CHF will first be
described.
[0068] In patients with CHF, neurohumoral compensatory mechanisms
are activated to maintain circulatory stability in a state of low
cardiac output. Neurohumoral activation, particularly activation of
the sympathetic nervous and renin-angiotensin-aldosterone systems,
works to maintain arterial pressure (via vasoconstriction) and
restore cardiac output (by increasing myocardial contractility,
heart rate, and intravascular volume). Such compensatory mechanisms
are beneficial in the short-term, but can become pathologic over
time. Persistent neurohumoral activation contributes significantly
to the progressive cardiovascular dysfunction seen in patients with
CHF. For example, inappropriate activation of the
renin-angiotensin-aldosterone system in CHF promotes salt and water
retention in the absence of hypovolemia, increasing preload and
increasing myocardial energy requirements on an already-failing
heart.
[0069] The autonomic nervous system regulates blood pressure by
augmenting the tonic rate of sympathetic discharge to smooth muscle
in the blood vessel wall. This tonic sympathetic stimulation
establishes and maintains vessel tone. Increasing sympathetic
discharge causes vasoconstriction, which increases total peripheral
resistance (TPR) and therefore increases blood pressure. Decreasing
sympathetic discharge causes vasodilation, which decreases TPR and
therefore decreases blood pressure. Sympathetic and parasympathetic
vasodilator innervation of blood vessels does not play a
significant role in determining TPR.
[0070] Baseline TPR is established and maintained via tonic
sympathetic outflow from the medullary vasomotor center (MVC) in
the rostral ventrolateral medulla (VLM). The MVC is the primary
site for integration of autonomic regulation of the cardiovascular
system. The MVC has reciprocal connections with higher CNS centers
(hypothalamus, cerebral cortex) and lower CNS centers (spinal cord
nuclei), and additionally receives sensory input from baroreceptors
and chemoreceptors.
[0071] The baroreceptor reflex pathway triggers rapid compensation
for changes in arterial pressure. Baroreceptors (high-pressure
mechanoreceptors in the carotid sinus, aortic arch, heart, and
lungs) sense blood pressure as "stretch" in the vessel wall.
Primary afferent neurons arising from baroreceptors project via the
vagal and glossopharyngeal nerves to the nucleus tractus solitarius
(NTS). Excitatory output from the NTS projects to the nucleus
ambiguus (vagal motor nucleus) and to the caudal VLM, which
activates GABAergic interneurons to relay inhibitory signals to the
rostral RVM. Efferent projections include 1) inhibitory vagal
projections to the heart and 2) sympathetic efferent projections
from the RVM to the heart and vasculature via the interomedial
column of spinal cord (IML) and sympathetic ganglia. Changes in
afferent (baroreceptor) firing frequency are mirrored in vagal
efferent firing frequency, and reversed in sympathetic efferent
firing frequency. Reflex changes in TPR are governed solely by
sympathetic activity. Reflex changes in heart rate are determined
by the balance between vagal and sympathetic efferent activity.
[0072] Increased arterial pressure causes an increase in
baroreceptor firing frequency, which increases inhibitory signaling
to the brain stem. This inhibition decreases sympathetic outflow,
which causes vasodilation and decreases heart rate, and also
increases parasympathetic outflow, which decreases heart rate. The
net result of the autonomic response to increased arterial pressure
is therefore a rapid, compensatory drop in blood pressure.
[0073] Decreased arterial pressure causes a decrease in
baroreceptor firing frequency, which decreases inhibitory signaling
to the brain stem. This increases sympathetic outflow, which causes
vasoconstriction and increasing heart rate, and also decreases
parasympathetic outflow, which increases heart rate. These effects
combine to increase cardiac output and TPR to prevent further
decreases in blood pressure and therefore maintain adequate
perfusion to vital organs.
[0074] Persistent activation of the sympathetic nervous system
begins in the early stages of CHF, and plays a significant role in
the natural history of the disease. Such sympathetic "overdrive"
attempts to compensate for reduced cardiac output but ultimately
accelerates the progression of the underlying ventricular
dysfunction. High circulating levels of norepinephrine (NE) induce
down-regulation or cardiac .beta.-adrenergic receptors, which
impairs cardiac inotropic and chronotropic response. At adrenergic
nerve endings, NE release is increased while re-uptake is
decreased. .alpha.2-receptors, which normally inhibit NE release,
are down-regulated. Increased circulating NE levels in heart
failure have been implicated in pathologic ventricular remodeling
and also in ventricular arrhythmias. Plasma NE levels directly
correlate with disease severity and mortality rate in patients with
CHF.
[0075] In the FIG. 6 embodiment, CHF treatment is achieved using
neurostimulation of features of the peripheral nervous system to
alter signals sent from baroreceptors of the arterial system to the
central nervous system to trigger vasodilation and to thus decrease
the heart's workload. In the FIG. 7 embodiment the neurostimulation
is directed towards the central nervous system so as to alter
signals sent from the central nervous system to prevertebral and
para vertebral sympathetic ganglia.
[0076] The method illustrated in FIG. 6 treats CHF by stimulating
baroreceptors in a manner that causes them to behave as they would
when stimulated through expansion of the associated vessel due to
an increase in arterial pressure, i.e. so that the baroreceptor
produces inhibitory signals that trigger decreases in sympathetic
tone, peripheral vascular resistance. and afterload.
[0077] Targeted baroreceptors include those in and/or around the
heart and large vessels. Tables 1 and 2 lists both barorecepter
(mechanoreceptors) and chemoreceptors that might be targeted using
electrical and/or chemical stimulation using the disclosed
embodiments.
TABLE-US-00001 TABLE 1 Mechanoreceptor Locations in Reflex Pathways
of Cardiovascular Regulation Inhibitory baroreceptors (most
vagal-mediated) Arterial baroreceptors: adventitia of vessel wall
in carotid sinuses (dilatation of vessel just above origin of
internal carotid artery) adventitia of vessel wall of aortic arch
Cardiopulmonary baroreceptors: atria, especially the right atrium,
especially at cavoatrial junctions (SVC, IVC, pulmonary veins) but
also diffusely distributed in atrial walls ventricular walls, left
> right coronary vasculature pulmonary artery (main pulmonary
artery and bifurcation) Excitatory baroreceptors
(sympathetic-mediated) Diffusely (and somewhat sparsely)
distributed throughout atria, ventricles, vena cavae, pulmonary
artery, pulmonary veins, pericardium, and aorta (above
diaphragm)
TABLE-US-00002 TABLE 2 Chemoreceptor Locations in Reflex Pathways
of Cardiovascular Regulation Chemoreceptors proper: sensitive to
.DELTA. P.sub.aO.sub.2, also sensitive to .DELTA. pH or .DELTA.
P.sub.aCO2 (esp. carotid body) Carotid body Aortic Body Peripheral
chemoreceptive cells: vagal-mediated or sympathetic- mediated;
opposing pathways triggered in same local region by short- lived
chemicals (bradykinin, prostaglandins) produced by hypoxic tissue
Juxtapulmonary capillaries, alveolar interstitium (J receptors;
pulmonary depressor chemoreflex) Coronary vasculature (coronary
depressor chemoreflex) and left ventricular wall Right ventricle
Atria Great veins Pulmonary artery Aorta Central chemoreceptors CNS
osmoreceptors (stimulate ADH secretion) located in hypothalamus
Persistent hypoxia .fwdarw. increase sympathetic output from
medullary vasomotor center
[0078] In the illustrated embodiment, electrical stimulation lead
14 extends superiorly from the device 12 and is electrically
coupled to electrode anchor 16b, which includes a plurality of
stimulating electrodes 26 positioned to contact the vessel walls
upon expansion of the anchor 16b. The lead 14 and electrode anchor
are positioned such that the associated electrodes are within the
internal jugular vein at the level of the carotid bifurcation. This
positioning allows the electrodes to stimulate the carotid
baroreceptors located in the carotid sinus adjacent to the internal
jugular vein. Multiple leads may be positioned at various
baroreceptor locations for multi-site stimulation.
[0079] In a modification to the FIG. 6 embodiment, stimulation may
instead or additionally be directed to afferent neurons that carry
signals from the baroreceptors to the central vasomotor center via
the glossopharyngeal nerve (which innervates the baroreceptors of
the carotid sinus) or the vagus nerve (which innervates the aortic
arch baroreceptors), for the purpose of enhancing the inhibitory
signaling of the baro-receptors.
[0080] Inhibition of the central vasomotor center can also be
increased by simulating baroreceptors in the atria or ventricles
(e.g. through the use of electrode leads situated in the heart), or
by stimulating baroreceptors within the lungs, and/or by
positioning the leads such that they will stimulate the afferent
vagal neurons that carry inhibitory signals from these
baroreceptors to the brain.
[0081] According to the method of FIG. 6, stimulation is preferably
delivered in response to feedback from one or more sensors
positioned on the implant itself, on a separate implant, or located
external to the body. Parameters that might be detected include but
are not limited to: (a) heart rate and/or Q-T interval determined
using an electronic sensor on the device body or lead or external
to the body; (b) aortic blood pressure and/or pulmonary artery
blood pressure, measured using one of various intravascular
pressure sensing techniques known in the art, including capacitive
pressure sensors, piezoelectric pressure sensors, temperature
differential pressure sensor, flow sensors, etc.; (c) left
ventricular chamber dimension determined using echo ultrasound, or
measurement of impedance between two closely spaced electrodes
within the heart (i.e. using impedance plethysmography
determinations); (d) cardiac output using a combination of chamber
dimension as determined in (c), plus flow, and heart rates measured
using conventional means; (e) chemical sensors for detecting,
sodium, calcium, various signaling hormones, AVO.sub.2 difference;
blood pH (including as an indicator of lactic acid levels in the
blood); blood gas levels (including blood 0.sub.2 and/or blood
CO.sub.2 levels).
[0082] The system might also be responsive to feedback from sensors
capable of detecting biochemical markers associated with CHF. Some
examples of markers targeted for detection might include: [0083]
(a) Triage Cardiac--any combination of a unique set of three
biochemical indicators of cardiac muscle necrosis: Mioglobine;
CK-MB and Cardiac Troponine I; (b) Tumor Necrosis
[0084] Factor. Elevated levels of the immune factor tumor necrosis
factor (TNFa) may be very strong and accurate predictors of a poor
outlook in CHF patients. This immune factor is known to be a potent
agent in the intlammatory process; (c) C-Reactive Protein (d) Brain
Natriuretic Peptide ("BNP")--a non-invasive, objective marker of
Congestive Heart Failure. With regard to BNP, research indicates
that [0085] The concentration of BNP increases with the severity of
CHF (precise correlation with NYHA classification). [0086] BNP
concentration has the positive correlation with end-diastolic
pressure in left ventricle. [0087] There is a reverse ratio between
BNP level and the function of left ventricle after heart
infarction. [0088] The increase of BNP level is associated with
increasing of Pulmonary Artery Wedge Pressure (precise
correlation), deterioration of LV diastolic and systolic functions,
LV Hypertrophy and Heart Infarction.
[0089] By using the same electrode location as shown in FIG. 6, the
carotid baroreceptor may instead be stimulated in a manner that
afferent signaling from the baroreceptor indicates increased
stretch of the vessel causing the body's feedback control system to
believe there is a volume overload condition and thus triggering
the efferent signaling to trigger increased natural diuresis. In
this example, electrical stimulation patterns would be chosen to
achieve the desired effect while at the same time selectively
blocking the downstream vasodilation effects. The embodiment shown
in FIG. 6 includes drug delivery leads 14b, 14c for delivering
suitable agents into the blood within the vasculature and/or the
heart. For example, the system may be used to deliver agents used
to treat symptoms of congestive heart failure (CHF), including
cardio-renal syndrome. Such agents may include agents within the
classes of positive inotropes, diuretics, vasodilators, and
cytokine effectors. Specific agents include: Dobutamine, Atrial
Natriuretic Peptide, Digoxin, Enoximone, Nesiritide, Tezosentan,
Bumetanide, Hydralazine, Alprostadil, Carvedilol, Enalaprilat,
Ambrisentan, and Levosimendan (sold by Abbott Laboratories under
the trade name Simdax). The leads 14b, 14e are coupled to a drug
reservoir/pump 40.
[0090] In the FIG. 6 arrangement, the leads are positionable to
deliver drugs to the kidneys, however, the leads may alternatively
be positioned elsewhere in the cardiovascular system, including
within the heart. In another embodiment, a two-device configuration
like that of FIG. 1C may be used so that electrodes can be
positioned in the internal jugular as shown in FIG. 6 as shown,
while a separate drug delivery device can be positioned in the
aterial system. This allows drug delivery leads 14b, 14c to be
anchored in the renal arteries, allowing blood flood to propel
drugs from the leads to the kidneys.
[0091] In the FIG. 7 embodiment, the neurostimulation device is
used to stimulate the central nervous system in order to augment
autonomic control of peripheral vascular resistance. The benefits
achieved using this embodiment are suitable for treatment of
congestive heart failure, as well as hypertension (essential and
secondary), diabetes mellitus, and other conditions.
[0092] Stimulation may be targeted to one or more of a variety of
neurological targets in the brain. In one example shown in FIG. 7,
stimulating electrodes are positioned in the brain to deliver
electrical stimulus that will inhibit the vasomotor center in the
rostral ventro-lateral medulla ("RVLM"). The vasomotor center in
the RVLM can be inhibited by low-level electrical stimulation to,
for example, inhibitory fibers to the nucleus tractus solitarius,
and/or stimulation of GABAergic interneurons projecting to the
RVLM. For example, an electrode lead can be passed through the
subclavian vein and the jugular vein, and then guided to, for
example, a superficial cranial vein. Afterwards, the surgeon
palpates the skin to find the lead, forms a small incision to gain
access to the lead, threads the lead through a treephine hole
drilled into the skull, and advances the lead towards the target
area within the brain. In some cases the target area may be
determined prior to device implantation using direct electrical
stimulation of the brain.
[0093] Alternatively, the electrical energy may be conducted
transvenously through the vessel walls towards the neurological
target without penetration of the vessel wall. Access to the
neurological target for direct or transvenous stimulation can be
gained via veins of the posterior fossa, the petrosal sinus and
petrosal veins, the vein of the middle cerebellar peduncle, the
lateral medullary and other medullary veins, the retro-olivary
vein, regional bridging veins, as well as through other
vessels.
[0094] In an alternative embodiment, rather than stimulating the
vasomotor center, stimulation may be used to inhibit efferent
neurons from the vasomotor center. In this example, stimulation
energy can be delivered to any point along the pathway between (and
including) the vasomotor center and the prevertebral and
paravertebral sympathetic ganglia.
[0095] FIGS. 8A through 11 illustrate methods for using an
intravascular stimulation device for treatment of sleep apnea. The
systems used in carrying out these methods preferably deliver
stimulation upon receipt of feedback indicative of a cessation in
breathing. Various parameters can be sensed for this purpose,
including but not limited to: (a) breathing movements using an
accelerometer to detect chest movement or a strain gauge to detect
chest expansion; (b) changes in lung volume using impedance
plethysmography to measure transthoracic impedance changes; (c)
changes in breathing efficiency using an intravascular chemical
sensor for detecting blood CO2 or O2 concentrations; (d) sleep
state using EEG electrodes positioned on the scalp or within the
brain; (e) facial movements, especially rapid eye movement, using
an accelerometer; (f) snoring using acoustic detection methods; (g)
muscle tone of specific throat structures using electrodes; (g)
changes in airway flow rates and pressures to monitor airway
patency.
[0096] The FIG. 8A embodiment uses phrenic nerve stimulation as a
means for treating sleep apnea. For example, in response to
detection of a threshold CO2 level by a CO2 sensor 60 positioned on
the device 12 or lead 14, one or more stimulating pulses are
delivered to the phrenic nerve, causing contraction of the
diaphragm to expand the lungs and to thus draw air into the lungs.
Similar device positioning might also be used for diaphragmatic
pacing to facilitate breathing in patients having neurological
injuries or disorders, such as motor neuron disease and spinal cord
injury, among others. Devices for diaphragmatic pacing might
include features allowing for rate adaptive breathing rate
modulation, allowing pacing to be responsive to feedback from one
or more sensors indicating various metabolic needs. Suitable
sensors include, for example, accelerometers for detecting patient
motion, heart rate monitors, and pCO.sub.2 and pO.sub.2
sensors.
[0097] In the illustrated embodiment, electrodes are anchored in
the left and right subclavian veins, near the phrenic nerves.
According to one electrode positioning method shown in FIG. 8B,
electrodes may be positioned directly in contact with the phrenic
nerve by extending an electrode lead 14 through an opening O formed
in a wall of a blood vessel, preferably at a location near the
phrenic nerve. A vascular sealing member or substance 62 may be
used to close the opening O in the region surrounding the lead to
minimize bleeding. The lead is positioned in contact with the
phrenic nerve, or embedded within the nerve tissue, such that by
energizing the electrode the nerve may be directly stimulated.
[0098] Alternatively, as shown in FIG. 8C, the lead may be
positioned within an intact vessel (e.g. a subclavian vein) at a
point at which the vessel crosses the phrenic nerve, thus allowing
conduction of the electrical stimuli from the electrode through the
vessel to the phrenic nerve.
[0099] FIG. 9 shows an alternative electrode arrangement suitable
for treating sleep apnea. According to this embodiment, electrodes
are positioned such that stimulation energy passes transvenously
through the walls of blood vessels that are in electrical contact
with the diaphragm, thus stimulating the diaphragm. Electrodes may
be positioned in the right and left hepatic veins as shown, or in
any other sites including but not limited to the inferior vena
cava. As with the FIG. 8A embodiment, this embodiment is also
suitable as a diaphragmatic pacer to facilitate breathing in
patients having motor neuron disease, spinal cord injury, or other
diseases/conditions.
[0100] In the FIG. 10 embodiment, electrical stimulation is
delivered to the hypoglossal nerve, which innervates the muscles of
the tongue. This embodiment may be useful for treating obstructive
sleep apnea in a patient whose tongue relaxes during sleep to a
point at which the tongue causes an obstruction of the airways.
Stimulating the hypoglossal nerve can increase the tone of the
muscles of the tongue, thus opening the airways.
[0101] In one exemplary electrode position shown in FIG. 10, energy
is conducted to the hypoglossal nerve using electrddes anchored in
the left and right internal jugular veins, near the points where
those veins cross the left and right hypoglossal nerves. If the
oropharyngeal muscles are instrumental in obstructing the airway
during sleep, the electrodes may be positioned to stimulate the
oropharyngeal muscles or the nerves that innervate them, so as to
contract those muscles away from the airway.
[0102] In another treatment which may be used for sleep apnea or
other conditions for which deep brain stimulation is suitable (e.g.
epilepsy), lead 14 may be extended into the brain (for example, as
described in connection with FIG. 7) for deep brain stimulation as
shown in FIG. 11A. Routes for passage of the lead into the brain
include, but are not limited to, the facial vein and the
retro-mandibular vein. FIG. 11B illustrates positioning of the
device 12 in the inferior vena cava, with the lead 14 extending
superiorly towards the brain.
[0103] The disclosed system may be used to deliver vagus nerve
stimulation for treatment of various diseases or conditions,
including but not limited to epilepsy, depression, Alzheimer's
disease, anxiety disorders (for example, obsessive compulsive
disorder), tourette syndrome, bulimia, and obesity. The FIG. 12
embodiment illustrates positioning of stimulation electrodes in the
internal jugular vein at a location from which energy from the
electrodes can be conducted through the jugular vein to the left
vagus nerve. Alternate electrode positions might also be used,
including the superior vena cava and the brachio-cephalic veins,
among others. Although FIG. 12 illustrates transvenous stimulation
of the nerve, it should be appreciated that with any of the
disclosed embodiments, direct stimulation may instead be employed
by passing the lead through the vessel wall and positioning it in
contact with the target neural structure.
[0104] Neurostimulation of cardiac parasympathetic nerves and
plexuses may be used to treat multiple types of aberrant heart
rates and rhythms. In one example shown in FIG. 13, of a
neurostimulation system is used for ventricular rate control during
atrial fibrillation. In this embodiment, the electrode is
positioned within the superior vena cava or in an alternate
location from which it can be used to stimulate adjacent cardiac
parasympathetic nerves to achieve ventricular rate control during
atrial fibrillation. Operating parameters may be selected to
deliver high-frequency (e.g. on the order of 50-250 Hz) nerve
stimuli during the atrial refractory period, thus preventing atrial
excitation during the adjacent nerve stimulation.
[0105] Neurostimulation of cardiac parasympathetic nerves and
plexuses may be accomplished either directly or transvenously, and
may be performed at multiple sites, including but not limited to
the superior vena cava, the inferior vena cava, and the coronary
sinus.
[0106] Alternative Applications
[0107] Suitable applications for use of these devices/systems
include, but are not limited to:
[0108] Deep brain stimulation (DBS) or cortical stimulation (alone
or in combination with drug delivery to the stimulated area) for
treatment of motor disorders including essential tremor,
Parkinson's disease, Dystonia, for stroke rehabilitation, as well
as other neurological disorders including obsessive conpulsive
disorder. epilepsy, depression, mood disorders, anxiety disorders,
pain and tinnitus. Stimulation might be delivered to regions of the
brain (e.g. the insula) to control addiction to substances or
behavior.
[0109] Occipital nerve stimulation (ONS) for treatment of
headaches;
[0110] Vagus nerve stimulation (VNS) for treatment of epilepsy,
depression, hypertension or heart failure;
[0111] Peripheral nerve stimulation (PNS) for treatment of chronic
pain;
[0112] Spinal cord stimulation (SCS) (alone or in combination with
drug delivery to the stimulated area) for treatment of chronic
pain, angina pain, peripheral vascular disease pain, malignant
pain, ALS symptoms, and symptoms of Huntington's disease;
[0113] Stimulation of nerves in the gastric system for obesity
treatment and gastroparesis;
[0114] Sacral or pelvic nerve stimulation for treatment of
incontinence, pelvic pain, and sexual dysfunction;
[0115] Stimulation of the pancreas to upregulate the production of
insulin or the electroporation of islet cells in treatment of
diabetes.
[0116] The devices disclosed might be used for non-neurological
therapy as well, such as the use of internal electrical stimulus to
promote healing of wounds on or within the body. For example,
targeted sympathetic blockade or parasympathetic nerve stimulation
may be used to increase regional blood flow in various target areas
to promote ulcer healing in patients with peripheral vascular
disease.
[0117] While various embodiments of the present invention have been
described above, it should be understood that they have been
presented by way of example, and not limitation. It will be
apparent to persons skilled in the relevant art that various
changes in tbrm and detail may be made therein without departing
from the spirit and scope of the invention. This is especially true
in light of technology and terms within the relevant art(s) that
may be later developed. Thus, the present invention should not be
limited by any of the above-described exemplary embodiments, but
should be defined only in accordance with the following claims and
their equivalents. The terms "first," "second" and the like, where
used herein, do not denote any order, quantity, or importance. In
references to "first blood vessel", "second blood vessel" etc., the
first and second blood vessels may be different blood vessels or
they may be the same blood vessel unless otherwise specified.
[0118] Any and all patents, patent applications and printed
publications referred to above are incorporated by reference.
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