U.S. patent application number 11/857268 was filed with the patent office on 2008-03-20 for apparatus and methods for in situ embolic protection.
This patent application is currently assigned to Cook Incorporated. Invention is credited to Michael P. DeBruyne, Andrew K. Hoffa, Jeffry S. Melsheimer, Sarah E. Reeves.
Application Number | 20080071307 11/857268 |
Document ID | / |
Family ID | 39092700 |
Filed Date | 2008-03-20 |
United States Patent
Application |
20080071307 |
Kind Code |
A1 |
DeBruyne; Michael P. ; et
al. |
March 20, 2008 |
APPARATUS AND METHODS FOR IN SITU EMBOLIC PROTECTION
Abstract
The present invention provides apparatus and methods for
treating a vascular condition by restoring patency to a vessel
while reducing the likelihood that emboli become dislodged into the
bloodstream. In a first embodiment, the apparatus comprises a graft
having proximal and distal regions, a first support member attached
to the distal region of the graft, and a second support member
attached to the proximal region of the graft. The first and second
support members may comprise first and second stents, respectively.
The first stent is deployed distal to a vascular condition, and the
second stent is deployed proximal to a vascular condition, such
that the graft spans the length of the vascular condition to entrap
emboli during treatment of the vascular condition. In an
alternative embodiment, the first stent is adapted to be deployed
within a vessel at a location distal to the vascular condition, and
the graft is adapted to be everted to form a pocket adapted to
entrap emboli dislodged during treatment of the vascular condition.
The second stent then may be subsequently deployed proximal to the
vascular condition, such that emboli trapped within the graft
pocket are effectively sealed off from the bloodstream.
Inventors: |
DeBruyne; Michael P.;
(Bloomington, IN) ; Hoffa; Andrew K.;
(Bloomington, IN) ; Melsheimer; Jeffry S.;
(Springville, IN) ; Reeves; Sarah E.; (Cory,
IN) |
Correspondence
Address: |
BRINKS HOFER GILSON & LIONE/CHICAGO/COOK
PO BOX 10395
CHICAGO
IL
60610
US
|
Assignee: |
Cook Incorporated
Bloomington
IN
|
Family ID: |
39092700 |
Appl. No.: |
11/857268 |
Filed: |
September 18, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60845577 |
Sep 19, 2006 |
|
|
|
Current U.S.
Class: |
606/200 ;
623/1.11; 623/1.13 |
Current CPC
Class: |
A61F 2002/075 20130101;
A61F 2250/0048 20130101; A61F 2/013 20130101; A61F 2/95 20130101;
A61F 2002/8486 20130101; A61F 2/07 20130101; A61F 2/011 20200501;
A61F 2/958 20130101 |
Class at
Publication: |
606/200 ;
623/1.11; 623/1.13 |
International
Class: |
A61M 29/00 20060101
A61M029/00; A61F 2/06 20060101 A61F002/06; A61F 2/84 20060101
A61F002/84 |
Claims
1. A method suitable for providing embolic protection during a
vascular procedure, the method comprising: providing a graft having
proximal and distal regions, a first support member attached to the
distal region of the graft, and a second support member attached to
the proximal region of the graft; deploying the first support
member to cause the first support member to engage an intima of the
vessel at a location distal to a vascular condition; treating the
vascular condition; and using the graft to entrap emboli dislodged
during treatment of the vascular condition.
2. The method of claim 1 further comprising everting the graft by
distally advancing the second support member with respect to the
first support member, thereby forming a pocket distal to the
vascular condition.
3. The method of claim 1 further comprising deploying the second
support member at a location proximal to the vascular condition,
thereby causing the graft to span the length of the vascular
condition and enclose the vascular condition.
4. The method of claim 1 further comprising: providing an
introducer having proximal and distal ends; using the introducer to
circumferentially enclose the first and second support members in a
delivery state; and proximally retracting the introducer with
respect to the first and second support members to cause the first
and second support members to self-expand into engagement with an
intima of the vessel at locations distal to and proximal to the
vascular condition, respectively.
5. The method of claim 4 further comprising treating the vascular
condition by performing balloon angioplasty on the vascular
condition using a balloon disposed on an exterior surface of the
introducer.
6. The method of claim 1 further comprising placing a stent over
the graft to secure the graft between the stent and the vascular
condition.
7. Apparatus suitable for providing embolic protection during a
vascular procedure, the apparatus comprising: a graft having inner
and outer surfaces, and further having proximal and distal regions;
a first support member attached to the distal region of the graft;
and a second support member attached to the proximal region of the
graft, wherein the first support member is adapted to be deployed
within a vessel at a location distal to a vascular condition, and
the graft is adapted to be everted to form a pocket adapted to
entrap emboli dislodged during treatment of the vascular
condition.
8. The apparatus of claim 7 wherein the first and second support
members comprise first and second stents, respectively.
9. The apparatus of claim 7 wherein the second support member is
adapted to be deployed within the vessel at a location proximal to
the vascular condition to cause the graft to span and enclose the
vascular condition.
10. The apparatus of claim 7 further comprising an introducer
having proximal and distal ends, wherein the introducer is
configured to circumferentially enclose the first support member,
the second support member and the graft in a delivery state.
11. The apparatus of claim 10 wherein the introducer comprises an
external surface and a balloon disposed thereon, the balloon
adapted to perform angioplasty on the vascular condition.
12. The apparatus of claim 10 wherein the first and second support
members comprise self-expanding support members that are adapted to
be deployed when the introducer is retracted proximally beyond the
respective first and second support members.
13. The apparatus of claim 10 further comprising a core member
having proximal and distal regions, wherein the first support
member, the second support member and the graft are disposed
circumferentially around the core member in the delivery state, and
wherein the core member comprises a lumen disposed between the
proximal and distal regions of the core member, the lumen being
configured to permit oxygenated fluid to flow upstream to arterial
vasculature during treatment of the vascular condition.
14. The apparatus of claim 13 further comprising a first pushing
member abutting the proximal end of the first support member and a
second pushing member abutting the proximal end of the second
support member.
15. The apparatus of claim 7 wherein at least a portion of the
graft comprises a material having a known porosity to permit
oxygenated fluid flow upstream, while substantially or completely
prohibiting the flow of emboli.
16. A method suitable for providing embolic protection during a
vascular procedure, the method comprising: providing a graft having
proximal and distal regions, a first support member attached to the
distal region of the graft, and a second support member attached to
the proximal region of the graft; deploying the first support
member to cause the first support member to engage an intima of the
vessel at a location distal to a vascular condition; everting the
graft by distally advancing the second support member with respect
to the first support member, thereby forming a pocket distal to the
vascular condition; treating the vascular condition; and using the
graft to entrap emboli dislodged during treatment of the vascular
condition.
17. The method of claim 16 further comprising deploying the second
support member at a location proximal to the vascular condition,
thereby causing the graft to span the length of the vascular
condition and enclose the vascular condition.
18. The method of claim 16 further comprising: providing an
introducer having proximal and distal ends; using the introducer to
circumferentially enclose the first and second support members in a
delivery state; and proximally retracting the introducer with
respect to the first and second support members to cause the first
and second support members to self-expand into engagement with an
intima of the vessel at locations distal to and proximal to the
vascular condition, respectively.
19. The method of claim 18 further comprising treating the vascular
condition by performing balloon angioplasty on the vascular
condition using a balloon disposed on an exterior surface of the
introducer.
20. The method of claim 16 further comprising placing a stent over
the graft to secure the graft between the stent and the vascular
condition.
Description
PRIORITY CLAIM
[0001] This invention claims the benefit of priority of U.S.
Provisional Application Ser. No. 60/845,577, entitled "Apparatus
and Methods for In Situ Embolic Protection," filed Sep. 19, 2006,
the disclosure of which is hereby incorporated by reference in its
entirety.
BACKGROUND
[0002] The present invention relates generally to apparatus and
methods for treating vascular conditions, and more specifically, by
treating the vascular conditions by restoring patency to the vessel
while reducing the likelihood that emboli become dislodged into the
bloodstream.
[0003] Atherosclerosis and other occlusive diseases are prevalent
among a significant portion of the population. In such diseases,
atherosclerotic plaque forms within the walls of the vessel and
blocks or restricts blood flow through the vessel. Atherosclerosis
commonly affects the coronary arteries, the aorta, the iliofemoral
arteries and the carotid arteries. Several serious conditions may
result from the restricted blood flow.
[0004] Various procedures are known for treating stenoses in the
arterial vasculature, such as the use of atherectomy devices,
balloon angioplasty and stenting. During an atherectomy procedure,
vascular plaque may be removed by inserting a catheter having a
rotating cutting blade into the vessel and using the blade to shave
away the plaque. During a balloon angioplasty procedure, a catheter
having a deflated balloon attached thereto is positioned across a
constricting lesion, and the balloon is then inflated to widen the
lumen to partially or fully restore patency to the vessel.
[0005] Stenting involves the insertion of a usually tubular member
into a vessel, and may be used alone or in conjunction with an
angioplasty procedure. Stents may be self-expanding or balloon
expandable. Self-expanding stents typically are delivered into a
vessel within a delivery sheath, which constrains the stent prior
to deployment. When the delivery sheath is retracted, the stent is
allowed to radially expand to its predetermined shape. If the stent
is balloon expandable, the stent typically is loaded onto a balloon
of a catheter, inserted into a vessel, and the balloon is inflated
to radially expand the stent.
[0006] One problem frequently encountered with atherectomy,
angioplasty and stenting procedures is that pieces of plaque are
often dislodged from the stenosis. Such pieces of plaque, referred
to as emboli, may flow away from the stenosis into other areas of
the vasculature and may be difficult to retrieve. Serious
complications, such as heart attack and stroke, may occur where the
emboli travel into the coronary, carotid or other arteries and
vessels.
[0007] Several techniques exist for retrieving emboli during a
medical procedure, such as deploying a filter within the
vasculature distal to the stenosis prior to treatment of the
stenosis to capture free-floating particles. Such embolic
filtration devices may comprise a mesh or net material coupled to a
plurality of expandable struts. The struts deploy radially outward
into engagement with the vessel wall, and the net is configured to
entrap emboli dislodged while the stenosis is treated.
[0008] Various problems exist with the use of such embolic
filtration devices. For example, the net may not fully capture all
embolic particles, especially relatively small fragments that may
escape through the net. Further, when relatively large embolic
particles are captured within the net and the filter device is
retracted into the delivery system, e.g., a catheter, such larger
particles may be difficult to retract within the confines of the
delivery system.
[0009] In view of the foregoing, there is a need for apparatus and
methods that effectively treat a vascular condition by restoring
patency to the vessel while reducing the likelihood that emboli
become dislodged into the bloodstream.
SUMMARY
[0010] The present invention provides apparatus and methods for
treating a vascular condition, such as a stenosis within a vessel,
by restoring patency to the vessel while reducing the likelihood
that emboli become dislodged into the bloodstream.
[0011] In a first embodiment, the apparatus comprises a graft
having proximal and distal regions, a first support member attached
to the distal region of the graft, and a second support member
attached to the proximal region of the graft. In this embodiment,
the first and second support members comprise first and second
stents, respectively. The first stent is adapted to be deployed
within a vessel at a location distal to a vascular condition, and
the second stent is adapted to be deployed within the vessel at a
location proximal to the vascular condition, such that the graft
spans the length of the vascular condition. The vascular condition
then may be treated, e.g., by performing balloon angioplasty, and
any emboli created during treatment of the vascular condition are
effectively contained by the deployed graft.
[0012] The first and second stents may comprise either
self-expanding or balloon-expandable stents. If self-expanding
stents are employed, the apparatus may further comprise an
introducer adapted to circumferentially enclose the first and
second stents in a delivery state. If the first and second stents
are balloon-expandable, the apparatus may further comprise a
balloon catheter adapted to deliver and deploy the first and second
stents into engagement with an intima of the vessel.
[0013] In an alternative embodiment, the apparatus comprises a
graft having proximal and distal regions, a first stent attached to
the distal region of the graft, and a second stent attached to the
proximal region of the graft, wherein the first stent is adapted to
be deployed within a vessel at a location distal to a vascular
condition, and the graft is adapted to be everted to form a pocket
adapted to entrap emboli dislodged during treatment of the vascular
condition. In this embodiment, the first stent is deployed to
engage an intima of the vessel at a location distal to a vascular
condition. Then, the graft is everted by distally advancing the
second stent with respect to the first stent, thereby forming a
pocket distal to the vascular condition. The vascular condition
then is treated, e.g., by performing balloon angioplasty, and any
emboli dislodged during treatment of the vascular condition are
entrapped within the pocket formed by the graft. Optionally, the
emboli may be aspirated from the pocket. In a next step, the second
stent is deployed at a location proximal to the vascular condition,
thereby causing the graft to span and enclose the vascular
condition, such that free-floating emboli will be trapped within
the confines of the graft.
[0014] In a preferred embodiment, at least a portion of the graft
comprises a collagenous extracellular matrix material to facilitate
adhesion of the graft with an intima of the vessel. More
preferably, the collagenous extracellular matrix material comprises
small intestinal submucosa.
[0015] Other systems, methods, features and advantages of the
invention will be, or will become, apparent to one with skill in
the art upon examination of the following figures and detailed
description. It is intended that all such additional systems,
methods, features and advantages be within the scope of the
invention, and be encompassed by the following claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The invention can be better understood with reference to the
following drawings and description. The components in the figures
are not necessarily to scale, emphasis instead being placed upon
illustrating the principles of the invention. Moreover, in the
figures, like referenced numerals designate corresponding parts
throughout the different views.
[0017] FIGS. 1-4 are side-sectional views showing apparatus and
method steps that may be performed in accordance with a first
embodiment of the present invention.
[0018] FIG. 5 is a side-sectional view illustrating an alternative
method for deploying the first and second support members of FIGS.
1-4.
[0019] FIGS. 6-11 are side-sectional views showing apparatus and
method steps that may be performed in accordance with an
alternative embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] In the present application, the term "proximal" refers to a
direction that is generally towards a physician during a medical
procedure, while the term "distal" refers to a direction that is
generally towards a target site within a patient's anatomy during a
medical procedure.
[0021] Referring now to FIGS. 1-4, apparatus and methods for
treating a vascular condition and reducing the migration of embolic
particles are described. In FIG. 1, apparatus 20 comprises graft 26
having inner and outer surfaces, and also having proximal and
distal regions. First and second support members are coupled to
graft 26. In the embodiment of FIGS. 1-4, the first and second
support members comprise first and second stents 22 and 24,
respectively. First stent 22 is attached to the distal region of
graft 26, while second stent 24 is attached to the proximal region
of graft 26. First and second stents 22 and 24 may be attached to
graft 26 by suturing, using adhesive, or other known techniques.
Further, both first and second stents 22 and 24 may be attached to
the inner surface of graft 26, as shown in FIGS. 1-4, or one or
both stents may be attached to the outer surface of graft 26.
[0022] Graft 26 may be made of a suitable biocompatible material,
such as woven Dacron, which is commonly employed in stent-grafts
for the treatment of aneurysms. Alternatively, graft 26 may
comprise Thoralon polyurethane. However, in a preferred embodiment,
as explained below, graft 26 may comprise a collagenous
extracellular matrix material (ECM), such as small intestinal
submucosa (SIS), which may facilitate attachment of graft 26 to the
intima of vessel V, as explained in detail below.
[0023] First and second stents 22 and 24 each comprise a
reduced-diameter delivery state, as shown in FIG. 1, and further
have an expanded state in which they are configured to expand
radially outward to engage an inner lumen of vessel V, as generally
shown in FIGS. 2-4 and explained in greater detail below. Various
types of stents may be used in conjunction with the present
invention. For example, first and second stents 22 and 24 may be
made from numerous metals and alloys, including stainless steel,
nitinol, cobalt-chrome alloys, amorphous metals, tantalum,
platinum, gold and titanium. The stents may also be made from
non-metallic materials, such as thermosets, thermoplastics and
other polymers. The structure of stents 22 and 24 may also be
formed in a variety of ways to provide a suitable intraluminal
support structure. For example, first and second stents 22 and 24
may be made from a woven wire structure, a laser-cut cannula,
individual interconnected rings, or any other type of stent
structure that is known in the art.
[0024] First and second stents 22 and 24 may also be designed to be
either balloon-expandable or self-expandable. In the embodiment of
FIGS. 1-4, first and second stents 22 and 24 are self-expandable
and are formed from a shape-memory alloy, such as nickel-titanium
(nitinol). In a delivery state, first and second stents 22 and 24
are radially constrained by introducer 40, which restricts radial
expansion of first and second stents 22 and 24 until retracted
proximally, as described in greater detail below.
[0025] Referring still to FIG. 1, apparatus 20 further preferably
comprises core member 30 having proximal and distal regions. The
distal region of core member 30 preferably comprises tapered end
33, which may be formed integrally with or attached to core member
30. Core member 30 may be formed of a suitable metal, for example,
stainless steel, or another appropriate material, such as a
biocompatible plastic.
[0026] In a first method step, apparatus 20 is delivered into
vessel V having a vascular condition, such as stenosis S, as shown
in FIG. 1. In the delivery state, first and second stents 22 and 24
are radially compressed around core member 30. First stent 22
preferably is disposed proximally adjacent to or abuts tapered end
33, as depicted in FIG. 1. First pushing member 42, which may be
formed integral with or attached circumferentially around core
member 30, is disposed just proximal to or abuts first stent 22.
Second stent 24 is disposed longitudinally spaced apart from first
stent 22. Second pushing member 44, which may be formed integral
with or attached circumferentially around core member 30, is
disposed proximal to or abuts second stent 24, as depicted in FIG.
1. All of the components, with the exception of tapered end 33, are
enclosed by introducer 40, as shown in FIG. 1.
[0027] Apparatus 20 is delivered into vessel V using known
techniques until first stent 22 is positioned distal to stenosis S,
as shown in FIG. 1. The positioning may be performed using
fluoroscopic guidance. Moreover, one of the components of apparatus
20 may comprise a radiopaque marker (not shown) to facilitate
positioning of the device. Preferably, at least one radiopaque
marker is disposed on first stent 22 and at least one marker is
disposed on second stent 24.
[0028] When the desired positioning is achieved, introducer 40 is
retracted proximally while core member 30 and first and second
pushing members 42 and 44 remain steady. When introducer 40 is
retracted proximally beyond first stent 22, first stent 22 will
expand radially outward into engagement with an inner surface of
vessel V at a location distal to stenosis S, as depicted in FIG. 2.
As introducer 40 is further retracted proximally, second stent 24
will expand radially outward into engagement with an inner surface
of vessel V at a location proximal to stenosis S. This causes graft
26 to span the length of stenosis S and fully enclose or cover the
stenosis, as depicted in FIG. 2. At this time, core member 30 and
introducer 40 may be retracted proximally and removed from the
patient's vessel.
[0029] In a next step, a suitable medical device may be inserted
into vessel V to treat the vascular condition while graft 26
effectively seals off stenosis S. For example, in FIG. 3, balloon
catheter 50 having proximal and distal regions and balloon 52
disposed on the distal region is advanced into vessel V over wire
guide 60. Balloon 52 is aligned with stenosis S and is inflated to
dilate stenosis S, as shown in FIG. 3. The inflation of balloon 52
may be achieved using an inflation fluid injected through an
inflation lumen (not shown), such as an annular inflation lumen, of
balloon catheter 50.
[0030] After balloon angioplasty has been performed, balloon 52 is
deflated and balloon catheter 50 and wire guide 60 are removed from
the patient's vessel. As shown in FIG. 4, first stent 22 remains
securely disposed distal to stenosis S, second stent 24 remains
securely disposed proximal to stenosis S, and graft 26 spans the
length of stenosis S to effectively seal off the stenosis, and the
patency within vessel V has been improved.
[0031] Advantageously, in accordance with one aspect, if any
embolic particles are dislodged during the step of treating
stenosis S, the emboli are effectively contained by graft 26, i.e.,
the emboli will not enter into the bloodstream. This technique is
expected to significantly reduce the likelihood of adverse future
occurrences, such as ischemic events.
[0032] If desired, a conventional stent (not shown) may also be
placed across stenosis S to help ensure that patency is maintained
within vessel V after the procedure. For example, the conventional
stent may comprise a balloon-expandable stent introduced in a
compressed state on balloon 52, such that when balloon 52 is
radially expanded to perform angioplasty, the conventional stent is
deployed and left inside vessel V. Alternatively, the conventional
stent may be introduced and deployed by other means, e.g., using a
self-expanding stent delivery system.
[0033] Referring now to FIG. 5, an alternative method for deploying
first and second stents 22 and 24 is shown. In the embodiment of
FIG. 5, first and second stents 22' and 24' are designed to be
balloon-expandable. The apparatus comprises balloon catheter 70,
which has proximal and distal ends and is configured to be advanced
over wire guide 60. Balloon catheter 70 may comprise first and
second balloons 72 and 74, which preferably are spaced apart by a
distance designed to correspond approximately to the distance by
which first and second stents 22' and 24' are spaced apart along
graft 26.
[0034] In FIG. 5, first and second stents 22' and 24' are secured
about first and second balloons 72 and 74, respectively, in a
collapsed delivery state. First and second balloons 72 and 74 are
then inflated, either simultaneously or sequentially, to radially
expand first and second stents 22' and 24', respectively, as shown
in FIG. 5. Once the stents engage the intima of vessel V and graft
26 effectively seals off stenosis S, first and second balloons 72
and 74 are deflated. One of the balloons, e.g., first balloon 72,
then may be aligned with stenosis S and inflated to perform
angioplasty on stenosis S. Optionally, the balloon that is intended
to perform angioplasty on stenosis S may have a different size or
configuration to facilitate the angioplasty procedure, e.g., first
balloon 72 may comprise a greater longitudinal length than second
balloon 74 to facilitate angioplasty, as shown in FIG. 5.
[0035] In still further alternative embodiments of the invention,
in lieu of first and second stents 22' and 24', the support members
coupled to graft 26 may comprise first and second inflatable rings.
The inflatable rings may comprise tubular-shaped members that are
adapted to be filled with a material such as a polymer, foam or
liquid. A suitable introducer having a lumen in communication with
the inflatable rings may be employed to inject the material into
the rings, thereby causing the rings to expand into engagement with
the intima of vessel V.
[0036] Alternatively, the support members coupled to graft 26 may
comprise adhesive rings. The adhesive rings, which are coupled to
the exterior surface of graft 26, may comprise tubular-shaped
members comprising a suitable adhesive material disposed on an
external surface of the rings. The adhesive rings may be
balloon-expanded, for example, as shown in FIG. 5. When the
external surface of the rings contact the intima of vessel V by
balloon expansion, the adhesive secures the rings to the vessel
wall.
[0037] Referring now to FIGS. 6-11, an alternative embodiment of
the invention is described. The components in FIGS. 6-11 generally
correspond to the components of FIGS. 1-4, except as noted below,
and are represented by similar reference numerals, e.g., first
stent 122, second stent 124 and graft 126 preferably are provided
in accordance with first stent 22, second stent 24 and graft 26,
respectively. Core member 130 is similar to core member 30, with a
main exception that it comprises lumen 136 formed between its
proximal and distal ends. Further, in the embodiment of FIGS. 6-11,
introducer 140 comprises proximal and distal regions and comprises
balloon 149 disposed on the distal region, as shown in FIG. 6.
[0038] In operation, apparatus 120 is introduced into a patient's
vessel V and positioned such that first stent 122 is disposed
distal to stenosis S, as depicted in FIG. 6. In a next step,
introducer 140 is retracted proximally beyond first stent 122 to
allow first stent 122 to expand radially outward and engage an
inner surface of vessel V, as shown in FIG. 7. At this time,
introducer 140 preferably is further advanced proximally to expose
a substantial portion of graft 126, as depicted in FIG. 7. However,
introducer 140 is not advanced proximally over second stent 124 at
this time.
[0039] Referring now to FIG. 8, in a next step, core member 130 and
introducer 140 are advanced simultaneously in a distal direction.
The simultaneous advancement of the components, while ensuring that
second stent 124 does not expand, causes graft 126 to become
everted and form pocket 155, as depicted in FIG. 8. At this time,
lumen 136 within core member 130 permits oxygenated fluid to flow
upstream to arterial vasculature during this segment of the
procedure. Further, balloon 149 becomes partially or fully aligned
with stenosis S.
[0040] Referring now to FIG. 9, in a further step, balloon 149 is
inflated to treat stenosis S. Inflation fluid may be provided via
inflation tube 162, which is disposed external to introducer 140
and placed in fluid communication with balloon 149. Alternatively,
inflation fluid may be provided via an inflation lumen formed
within an exterior wall of introducer 140.
[0041] During treatment of stenosis S, embolic particles may become
dislodged into vessel V. In accordance with one aspect, if any
embolic particles are dislodged during the step of treating
stenosis S, the emboli are effectively contained by pocket 155,
which has been formed by the eversion of graft 126. The emboli will
not enter into the bloodstream to flow upstream to arterial
vasculature, which is expected to significantly reduce the
likelihood of adverse future occurrences, such as ischemic events.
Optionally, graft 126 may be slightly porous, thus acting more like
a conventional filter and allowing for some blood perfusion.
[0042] Referring now to FIG. 10, in a next step, balloon 149 is
deflated after satisfactory treatment of stenosis S. Then, core
member 130 and introducer 140 are retracted simultaneously in a
proximal direction, such that graft 126 is no longer everted and
second stent 124 is disposed proximal to stenosis S. It should be
noted that any embolic particles previously dislodged are still
safely confined within vessel V because first stent 122 remains
sealed against the vessel wall. Preferably, at this time,
aspiration may be provided to vessel V to remove some or all of the
emboli confined within pocket 155.
[0043] Introducer 140 is then further retracted proximally, white
core member 130 and second pushing member 142 are held steady, to
expose second stent 124 and allow its expansion against the inner
wall of vessel V, as shown in FIG. 11. At this time, graft 126 is
securely sealed against the inner wall of vessel V. Any embolic
particles that had been confined within pocket 155, and not
aspirated, are effectively sealed off between graft 126 and the
intima of the vessel wall. As noted above, a conventional stent may
be subsequently deployed to press against the inner surface of
graft 126 to help maintain patency within vessel V.
[0044] Alternatively, a conventional balloon-expandable stent may
be carried on the exterior surface of balloon 149. When balloon 149
is expanded, the balloon-expandable stent is deployed against the
inner wall of vessel V. Subsequently, graft 26 is placed over
stenosis S and the balloon-expandable stent. In effect, the
balloon-expandable stent will be disposed between graft 26 and the
inner wall of vessel V, at a location between first and second
stents 122 and 124.
[0045] Preferably, grafts 26 and 126 in the above-described
embodiments comprise a collagenous extracellular matrix material
(ECM), such as small intestinal submucosa (SIS), which may
facilitate attachment of grafts 26 and 126 to the intima of vessel
V. Grafts 26 and 126 preferably are manufactured using a material,
or comprise a coating, that facilitates attachment of an outer
surface of the grafts to the intima of vessel V. In a preferred
embodiment, reconstituted or naturally-derived collagenous
materials can be used in the present invention. Such materials that
are at least bioresorbable will provide an advantage in the present
invention, with materials that are bioremodelable and promote
cellular invasion and ingrowth providing particular advantage.
[0046] Suitable bioremodelable materials can be provided by
collagenous ECMs possessing biotropic properties, including in
certain forms angiogenic collagenous extracellular matrix
materials. For example, suitable collagenous materials include ECMs
such as submucosa, renal capsule membrane, dermal collagen, dura
mater, pericardium, fascia lata, serosa, peritoneum or basement
membrane layers, including liver basement membrane. Suitable
submucosa materials for these purposes include, for instance,
intestinal submucosa, including SIS, stomach submucosa, urinary
bladder submucosa, and uterine submucosa.
[0047] As prepared, the submucosa material and any other ECM used
may optionally retain growth factors or other bioactive components
native to the source tissue. For example, the submucosa or other
ECM may include one or more growth factors such as basic fibroblast
growth factor (FGF-2), transforming growth factor beta (TGF-beta),
epidermal growth factor (EGF), and/or platelet derived growth
factor (PDGF). As well, submucosa or other ECM used in the
invention may include other biological materials such as heparin,
heparin sulfate, hyaluronic acid, fibronectin and the like. Thus,
generally speaking, the submucosa or other ECM material may include
a bioactive component that induces, directly or indirectly, a
cellular response such as a change in cell morphology,
proliferation, growth, protein or gene expression.
[0048] Submucosa or other ECM materials of the present invention
can be derived from any suitable organ or other tissue source,
usually sources containing connective tissues. The ECM materials
processed for use in the invention will typically include abundant
collagen, most commonly being constituted at least about 80% by
weight collagen on a dry weight basis. Such naturally-derived ECM
materials will for the most part include collagen fibers that are
non-randomly oriented, for instance occurring as generally uniaxial
or multi-axial but regularly oriented fibers. When processed to
retain native bioactive factors, the ECM material can retain these
factors interspersed as solids between, upon and/or within the
collagen fibers. Particularly desirable naturally-derived ECM
materials for use in the invention will include significant amounts
of such interspersed, non-collagenous solids that are readily
ascertainable under light microscopic examination with specific
staining. Such non-collagenous solids can constitute a significant
percentage of the dry weight of the ECM material in certain
inventive embodiments, for example at least about 1%, at least
about 3%, and at least about 5% by weight in various embodiments of
the invention.
[0049] The submucosa or other ECM material used in the present
invention may also exhibit an angiogenic character and thus be
effective to induce angiogenesis in a host engrafted with the
material. In this regard, angiogenesis is the process through which
the body makes new blood vessels to generate increased blood supply
to tissues. Thus, angiogenic materials, when contacted with host
tissues, promote or encourage the infiltration of new blood
vessels. Methods for measuring in vivo angiogenesis in response to
biomaterial implantation have recently been developed. For example,
one such method uses a subcutaneous implant model to determine the
angiogenic character of a material. When combined with a
fluorescence microangiography technique, this model can provide
both quantitative and qualitative measures of angiogenesis into
biomaterials.
[0050] Further, in addition or as an alternative to the inclusion
of native bioactive components, non-native bioactive components
such as those synthetically produced by recombinant technology or
other methods, may be incorporated into the submucosa or other ECM
tissue. These non-native bioactive components may be
naturally-derived or recombinantly produced proteins that
correspond to those natively occurring in the ECM tissue, but
perhaps of a different species (e.g. human proteins applied to
collagenous ECMs from other animals, such as pigs). The non-native
bioactive components may also be drug substances. Illustrative drug
substances that may be incorporated into and/or onto the ECM
materials used in the invention include, for example, antibiotics
or thrombus-promoting substances such as blood clotting factors,
e.g. thrombin, fibrinogen, and the like. These substances may be
applied to the ECM material as a premanufactured step, immediately
prior to the procedure (e.g. by soaking the material in a solution
containing a suitable antibiotic such as cefazolin), or during or
after engraftment of the material in the patient.
[0051] Submucosa or other ECM tissue that may be used in the
invention is preferably highly purified, for example, as described
in U.S. Pat. No. 6,206,931 to Cook et al. Thus, preferred ECM
material will exhibit an endotoxin level of less than about 12
endotoxin units (EU) per gram, more preferably less than about 5 EU
per gram, and most preferably less than about 1 EU per gram. As
additional preferences, the submucosa or other ECM material may
have a bioburden of less than about 1 colony forming units (CFU)
per gram, more preferably less than about 0.5 CFU per gram. Fungus
levels are desirably similarly low, for example less than about 1
CFU per gram, more preferably less than about 0.5 CFU per gram.
Nucleic acid levels are preferably less than about 5 .mu.g/mg, more
preferably less than about 2 .mu.g/mg, and virus levels are
preferably less than about 50 plaque forming units (PFU) per gram,
more preferably less than about 5 PFU per gram. These and
additional properties of submucosa or other ECM tissue taught in
U.S. Pat. No. 6,206,931 may be characteristic of the submucosa
tissue used in the present invention.
[0052] If grafts 26 and 126 of the above-mentioned embodiments
employ SIS material, then in order to pressurize the SIS material,
it may be treated with a biodegradable solution such as
polyvinylpyrrolidone (PVP). As will be apparent, the entirety of
grafts 26 and 126 may be manufactured from an ECM material such as
SIS, or alternatively, selected portions may be manufactured from
the ECM material or may be selectively coated with the material to
promote localized fusion with vessel V.
[0053] While various embodiments of the invention have been
described, it will be apparent to those of ordinary skill in the
art that many more embodiments and implementations are possible
within the scope of the invention. Accordingly, the invention is
not to be restricted except in light of the attached claims and
their equivalents. Moreover, the advantages described herein are
not necessarily the only advantages of the invention and it is not
necessarily expected that every embodiment of the invention will
achieve all of the advantaged described.
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