U.S. patent application number 09/954789 was filed with the patent office on 2002-03-21 for methods for treating endoleaks during endovascular repair of abdominal aortic aneurysms.
Invention is credited to Cragg, Andrew H., Dolmatch, Bart, Greff, Richard J., Ricci, Charlie.
Application Number | 20020034493 09/954789 |
Document ID | / |
Family ID | 23042637 |
Filed Date | 2002-03-21 |
United States Patent
Application |
20020034493 |
Kind Code |
A1 |
Ricci, Charlie ; et
al. |
March 21, 2002 |
Methods for treating endoleaks during endovascular repair of
abdominal aortic aneurysms
Abstract
Disclosed are methods for treating endoleaks arising from
endovascular repair of abdominal aortic aneurysms. The disclosed
methods involve the in situ sealing of endoleaks after placement of
an endovascular prostheses in the abdominal aorta. Sealing of
endoleaks is achieved by injection of either a biocompatible
polymer or prepolymer fluid composition into the endoleak which
composition in situ solidifies to seal the leak. Preferably, the
biocompatible fluid composition comprises a contrast agent to allow
the clinician to visualize the sealing process.
Inventors: |
Ricci, Charlie; (Mission
Viejo, CA) ; Dolmatch, Bart; (Hunting Valley, OH)
; Cragg, Andrew H.; (Edina, MN) ; Greff, Richard
J.; (St. Pete Beach, FL) |
Correspondence
Address: |
Robert E. Krebs
BURNS, DOANE, SWECKER & MATHIS, L.L.P.
P.O. Box 1404
Alexandria
VA
22313-1404
US
|
Family ID: |
23042637 |
Appl. No.: |
09/954789 |
Filed: |
September 12, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09954789 |
Sep 12, 2001 |
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09528656 |
Mar 20, 2000 |
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09528656 |
Mar 20, 2000 |
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09273120 |
Mar 19, 1999 |
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6203779 |
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Current U.S.
Class: |
424/78.37 ;
514/57 |
Current CPC
Class: |
A61L 24/06 20130101;
A61L 24/06 20130101; C08L 29/04 20130101; C08L 33/04 20130101; C08L
1/12 20130101; A61B 17/0057 20130101; A61B 2017/00575 20130101;
A61L 24/08 20130101; A61B 2090/3933 20160201; A61L 2430/36
20130101; A61L 24/001 20130101; Y10S 524/916 20130101; A61F 2/06
20130101; A61L 24/08 20130101; A61B 2090/3937 20160201; A61L 24/06
20130101; A61B 17/00491 20130101 |
Class at
Publication: |
424/78.37 ;
514/57 |
International
Class: |
A61K 031/78; A61K
031/717 |
Claims
What is claimed is:
1. A method for sealing endoleaks in a patient arising from
endovascular repair of abdominal aortic aneurysms which method
comprises: identifying an abdominal aortic aneurysm in a patient;
endovascularly repairing said aneurysm by catheter delivery of an
endovascular prosthesis to the site of said aneurysm thereby
inhibiting blood flow into the aneurysm; identifying one or more
endoleaks in a patient; and delivering through a microcatheter to
the site or sites of endoleaks in said patient a sufficient amount
of a fluid composition comprising a biocompatible solvent and a
biocompatible polymer under conditions wherein the fluid
composition forms a coherent adhesive mass in situ thereby sealing
the endoleaks.
2. The method according to claim 1 wherein said biocompatible
polymer is selected from the group consisting of cellulose acetate
polymers, ethylene vinyl alcohol copolymers and polyacrylates.
3. The method according to claim 2 wherein said biocompatible
polymer is a cellulose acetate polymer or an ethylene vinyl alcohol
copolymer.
4. The method according to claim 1 wherein said biocompatible
solvent is selected from the group consisting of dimethylsulfoxide,
ethanol, ethyl lactate, and acetone.
5. The method according to claim 4 wherein said biocompatible
solvent is dimethylsulfoxide.
6. The method according to claim 1 wherein the composition further
comprises a contrast agent.
7. The method according to claim 6 wherein said contrast agent is a
water insoluble contrast agent.
8. The method according to claim 7 wherein said water insoluble
contrast agent is selected from the group consisting of tantalum,
tantalum oxide, tungsten, and barium sulfate.
9. The method according to claim 7 wherein said water insoluble
contrast agent is characterized by having an average particle size
of about 10 .mu.m or less.
10. The method according to claim 6 wherein said contrast agent is
a water soluble contrast agent.
11. The method according to claim 10 wherein said water soluble
contrast agent is selected from the group consisting of
metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and
meglumine.
12. A method for sealing endoleaks in a patient arising from
endovascular repair of abdominal aortic aneurysms which method
comprises: identifying an abdominal aortic aneurysm in a patient;
endovascularly repairing said aneurysm by catheter delivery of an
endovascular prosthesis to the site of said aneurysm thereby
inhibiting blood flow into the aneurysm; identifying one or more
endoleaks in a patient; and delivering through a microcatheter to
the site or sites of endoleaks in said patient a sufficient amount
of a fluid composition comprising a biocompatible prepolymer, a
water insoluble contrast agent and, when necessary to provide for a
fluid composition, a biocompatible solvent wherein said delivery is
conducted under conditions wherein the fluid composition forms a
coherent adhesive mass in situ thereby sealing the endoleaks.
13. The method according to claim 12 wherein said water insoluble
contrast agent is selected from the group consisting of tantalum,
tantalum oxide, tungsten, and barium sulfate.
14. The method according to claim 12 wherein said water insoluble
contrast agent is characterized by having an average particle size
of about 10 .mu.m or less.
15. The method according to claim 12 wherein the biocompatible
prepolymer is selected from the group consisting of cyanoacrylates,
hydroxyethyl methacrylate and silicon prepolymers.
16. A kits of parts for use in sealing endoleaks arising from
endovascular repair of an aneurysm which comprises: (a) a fluid
composition which forms a coherent mass in the presence of blood
which mass adheres to the vascular surface and/or the surface of
the endovascular prosthesis; (b) a catheter suitable for delivering
the fluid composition to an endoleak site formed from endovascular
repair of an aneurysm; and (c) a catheter suitable for delivering
an endovascular prosthesis to the aneurysm.
17. The kit of parts according to claim 16 which kit further
comprises an endovascular prosthesis.
18. A kits of parts for use in sealing endoleaks arising from
endovascular repair of an aneurysm which comprises: (a) a fluid
composition which forms a coherent mass in the presence of blood
which mass adheres to the vascular surface and/or the surface of
the endovascular prosthesis; (b) a catheter suitable for delivering
the fluid composition to an endoleak site formed from endovascular
repair of an aneurysm; and (c) an endovascular prosthesis.
19. The kit of parts according to claim 18 which kit further
comprises a catheter suitable for delivering an endovascular
prosthesis to the aneurysm.
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This application is a continuation-in-part of U.S. patent
application Ser. No. 09/273,120 filed Mar. 19, 1999 which
application is incorporated herein by reference in its
entirety.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] This invention is directed to methods for treating endoleaks
arising from endovascular repair of abdominal aortic aneurysms.
Specifically, the methods of this invention involve the in situ
sealing of endoleaks after placement of an endovascular prostheses
in the abdominal aorta. Sealing of endoleaks is achieved by
injection of a biocompatible fluid composition at the site of the
endoleak which composition in situ solidifies and adheres to the
vascular and/or prosthetic wall to seal the leak. Preferably, the
biocompatible fluid composition comprises a contrast agent to allow
the clinician to visualize the sealing process.
[0005] 2. References
[0006] The following publications, patent applications and patents
are cited in this application as superscript numbers:
[0007] 1 May, et al., "Concurrent Comparison of Endoluminal Versus
Open Repair in the Treatment of Abdominal Aortic Aneurysms:
Analysis of 303 Patients by Life Table Method", J. Vasc. Surg.
27(2):213-221 (1998)
[0008] 2 White, et al., J. Endovasc. Surg., 3:124-125 (1996)
[0009] 3 Marty, et al., "Endoleak After Endovascular Graft Repair
of Experimental Aortic Aneurysms: Does Coil Embolization with
Angiographic "Seal " Lower Intraaneursymal Pressure", J. Vasc.
Surg., 27(3):454-462 (1998)
[0010] 4 Money, et al., "Perioperative Charge Comparison and
Endovascular Abdominal Aortic Aneurysm Repair", JPV 1.1-1.2,
Presented at the 6.sup.th Annual Symposium on Current Issues and
New Techniques in Interventional Radiology at New York, N.Y. in
November, 1998
[0011] 5 Beebe, et al., "Current Status of the United States
Vanguard.TM. Endograft Trial", JPVA 2.1-2.3, Presented at the
6.sup.th Annual Symposium on Current Issues and New Techniques in
Interventional Radiology at New York, N.Y. in November, 1998
[0012] 6 Hopkinson, et al., "Current Critical Problems, New
Horizons and Techniques in Vascular and Endovascular Surgery",
JPIII 4.1-4.2, Presented at the 6.sup.th Annual Symposium on
Current Issues and New Techniques in Interventional Radiology at
New York, N.Y. in November, 1998
[0013] 7 Kinugasa, et al., "Direct Thrombosis of Aneurysms with
Cellulose Acetate Polymer", J. Neurosurg., 77:501-507 (1992)
[0014] 8 Greff, et al., U.S. Pat. No. 5,667,767 for "Novel
Compositions for Use in Embolizing Blood Vessels", issued Sep. 16,
1997
[0015] 9 Greff, et al., U.S. Pat. No. 5,580,568 for "Cellulose
Diacetate Compositions for Use in Embolizing Blood Vessels", issued
Dec. 3, 1996
[0016] 10 Kinugasa, et al., "Early Treatment of Subarachnoid
Hemorrhage After Preventing Rerupture of an Aneurysm", J.
[0017] Neurosurg., 83:34-41 (1995)
[0018] 11 Kinugasa, et al., "Prophylactic Thrombosis to Prevent New
Bleeding and to Delay Aneurysm Surgery", Neurosurg., 36:661
(1995)
[0019] 12 Taki, et al., "Selection and Combination of Various
Endovascular Techniques in the Treatment of Giant Aneurysms", J.
Neurosurg., 77:37-42 (1992)
[0020] 13 Evans, et al., U.S. patent application Ser. No.
08/802,252 for "Novel Compositions for Use in Embolizing Blood
Vessels", filed Feb. 19, 1997.
[0021] 14 Castaneda-Zuniga, et al., Interventional Radiology, in
Vascular Embolotherapy, Part 1, 1:9-32, Williams & Wilkins,
Publishers (1992)
[0022] 15 Rabinowitz, et al., U.S. Pat. No. 3,527,224, for "Method
of Surgically Bonding Tissue Together", issued Sep. 8, 1970
[0023] 16 Hawkins, et al., U.S. Pat. No. 3,591,676, for "Surgical
Adhesive Compositions", issued Jul. 6, 1971
[0024] 17 Parodi, "Endovascular AAA Stent Grafts: Technology,
Training and Proper Patient Selection, JPVA 1.1- 1.2 Presented at
the 6.sup.th Annual Symposium on Current Issues and New Techniques
in Interventional Radiology at New York, N.Y. in November, 1998
[0025] 18 van Schie, et al., "Successful Embolization of Persistent
Endoleak from a Patent Inferior Mesenteric Artery", J.
[0026] Endovasc. Surg., 4:312-315 (1997)
[0027] 19 Walker, et al., "A Study of the Patency of the Inferior
Mesenteric and Lumbar Arteries in the Incidence of Endoleak
Following Endovascular Repair of Infra-renal Aortic Eneurysms",
Clinical Radiology, 53:593-595 (1998)
[0028] All of the above publications, patent applications and
patents are herein incorporated by reference in their entirety to
the same extent as if each individual publication, patent
application or patent was specifically and individually indicated
to be incorporated by reference in its entirety.
STATE OF THE ART
[0029] Abdominal aortic aneurysms (AAA) represents a serious
medical challenge and, when left untreated, eventual rupture of the
aneurysm has significant morbidity associated therewith. When
feasible, open surgery to repair the aortic aneurysm has been shown
to be clinically successful..sup.1 However, open surgery is often
not feasible especially in patients suffering from severe cardiac
disease, renal disease or other conditions which contraindicate
open surgery. For example, conventional exposure of the infrarenal
aorta necessitates a large abdominal incision, mobilization of the
abdominal viscera, and retroperitoneal dissection which are
associated with complications such as renal failure,
pseudoaneurysms and bleeding. Infrarenal aortic clamping is also
associated with an increased cardiac demand including an increase
in left ventricular end diastolic volume and may be related to
cardiac mortality.
[0030] Less invasive methods for treating abdominal aortic
aneurysms avoid many of these problems and additionally result in
reduced patient discomfort, reduced hospital stays and reduced care
intensity..sup.5 Endovascular grafts have been investigated as one
example of a less invasive method for the treatment of aneurysmal
aortic disease. When compared to open surgery, endovascular
grafting provides similar perioperative mortality rates
notwithstanding the fact that endovascular grafting is often
performed with individuals who are not candidates for open surgery
due to one or more medical conditions which preclude such
surgery..sup.1,4 One of the main concerns regarding endovascular
grafting is the continued blood flow into the aneurysm after
grafting which blood flow is termed in the art as an
endoleak..sup.2 Endoleaks have been reported in from about 7 to
about 37% of endovascular aortic aneurysm repairs.sup.3 with some
reports placing this number as high as 44%.
[0031] Specifically, endovascular grafting requires catheter
placement of an endovascular prosthesis at the abdominal aortic
aneurysm site. Endoleaks arising after such grafting may be caused
by incomplete sealing between the endovascular prosthesis and the
aortic wall or by defects within the endovascular prosthesis. In
addition, back bleeding from patent lumbar and inferior mesenteric
arteries following placement of the endovascular prostheses in the
aorta has also been recited as a potential cause of
endoleaks..sup.6 There is uniform agreement that large endoleaks
that lead to aneurysm enlargement necessitate treatment in order to
prevent aneurysm rupture. It is also reported that the size of the
endoleak does not appear to be a relevant factor for pressure
transmission into the aneurysm..sup.3
[0032] There are a variety of prophylactic and therapeutic
treatment regimens for endoleaks reported in the literature.
Prophylactic methods of inhibiting endoleaks by embolizing
vasculature leading to the aneurysm, evidently with metallic coils,
have been suggested and dismissed in an article by Walker, et
al..sup.19 Therapeutic methods for endovascular repair include
placement of additional stents within the prosthesis; insertion of
metallic coils into the aneurysm space to induce thrombosis
therein; and embolization of the inferior mesenteric artery using a
prepolymer/water soluble contrast agent composition..sup.18
[0033] The goal of such treatments is complete exclusion of the
aneurysm from systemic blood flow. While complete exclusion is
desirable, a secondary goal is to reduce intraaneursymal pressure
(IAP) from blood flow into the aneurysm to acceptable levels
thereby inhibiting the likelihood of rupture. In cases where no
endoleaks arose after endovascular grafting, the mean LAP has been
reported to be reduced by about 65%. However, when endoleaks arise,
it is reported that the mean IAP, while initially decreasing
significantly, stabilized after a week at a reduction of only 22%.
Moreover, the use of coils to induce thrombosis and thereby reduce
IAP did not have any significant impact on the IAP.
[0034] In view of existing problems associated with endovascular
repair of endoleaks, the accepted treatment for these endoleaks is
open surgery. However, the mortality rates for open surgery of
endoleaks is higher than either initial open surgery for the
abdominal aortic aneurysm or for the initial endovascular repair of
the aneurysm.
[0035] In view of the above, reliable endovascular methods to
inhibit endoleaks after endovascular graft repair of abdominal
aortic aneurysms is desirable.
SUMMARY OF THE INVENTION
[0036] This invention is directed to methods for treating endoleaks
arising from endovascular repair of abdominal aortic aneurysms.
These methods provide for delivery of a fluid composition to the
sites of endoleaks in the abdominal aorta which fluid composition,
in situ, forms a coherent solid mass which adheres to vascular
and/or prosthetic wall to seal the endoleak.
[0037] In a preferred embodiment, the fluid composition comprises a
biocompatible polymer, a biocompatible solvent and a contrast agent
to allow the clinician to visualize the procedure. In a further
preferred embodiment, the contrast agent is a water insoluble
contrast agent characterized by having an average particle size of
about 10 .mu.m or less.
[0038] In another preferred embodiment, the fluid composition
comprises a biocompatible prepolymer and a contrast agent which,
again, is employed to allow the clinician to visualize the
procedure. In a further preferred embodiment, the contrast agent is
a water insoluble contrast agent characterized by having an average
particle size of about 10 .mu.m or less.
[0039] Accordingly, in one of its method aspects, this invention
provides a method for sealing endoleaks in a patient arising from
endovascular repair of abdominal aortic aneurysms which method
comprises:
[0040] identifying an abdominal aortic aneurysm in a patient;
[0041] endovascularly repairing said aneurysm by catheter delivery
of an endovascular prosthesis to the site of said aneurysm thereby
inhibiting blood flow into the aneursym;
[0042] identifying one or more endoleaks in said patient; and
[0043] delivering to the site or sites of the endoleak in said
patient a sufficient amount of a fluid composition comprising a
biocompatible solvent and a biocompatible polymer under conditions
wherein the fluid composition forms a coherent adhesive mass in
situ at said site or sites thereby sealing the endoleaks.
[0044] In one preferred embodiment, the fluid composition further
comprises a contrast agent to permit the clinician to detect the
composition in vivo. The contrast agent can be either water soluble
or water insoluble and preferably is water insoluble.
[0045] In another preferred embodiment, the fluid composition is
delivered by a microcatheter, by a needle or any other access
device.
[0046] Methods further comprising the step of delivering a
detectable agent, such as a contrast agent, through the catheter or
needle after it has been inserted into the artery and detecting the
agent to confirm that the catheter has the proper placement prior
to delivery of the fluid composition to the site of the endoleak
are also provided.
[0047] In another of its method aspects, this invention is directed
to a method for treating abdominal aortic aneurysms in a patient
which method comprises:
[0048] identifying an abdominal aortic aneurysm in a patient;
[0049] endovascularly repairing said aneurysm by catheter delivery
of an endovascular prosthesis to the site of said aneurysm thereby
inhibiting blood flow into the aneurysm;
[0050] identifying the presence of one or more endoleaks in said
patient;
[0051] delivering to the site or sites of endoleaks in said patient
a sufficient amount of a fluid composition comprising a
biocompatible prepolymer and a water insoluble contrast agent under
conditions wherein the fluid composition forms a coherent mass in
situ which adheres to the walls of the vascular site and/or
prosthesis thereby sealing the endoleaks.
[0052] In a preferred embodiment, the fluid composition is
delivered by either a microcatheter or by a needle.
[0053] This invention is also directed to kits of parts for use in
endovascular treatment of aneurysms in a patient including sealing
of endoleaks arising from such repair. In one embodiment, this kit
comprises the following components:
[0054] (a) a fluid composition which is selected from the group
consisting of (i) a biocompatible polymer and a biocompatible
solvent and (ii) a biocompatible prepolymer and a water insoluble
contrast agent which fluid composition forms a coherent mass in the
presence of blood which mass adheres to the vascular surface and/or
the surface of the endovascular prosthesis;
[0055] (b) a catheter suitable for delivering the fluid composition
to an endoleak site formed from endovascular repair of an aneurysm;
and
[0056] (c) a catheter suitable for delivering an endovascular
prosthesis to the aneurysm.
[0057] In a preferred embodiment, this kit further comprises an
endovascular prosthesis.
[0058] In another embodiment, this kit comprises the following
components:
[0059] (a) a fluid composition which is selected from the group
consisting of (i) a biocompatible polymer and a biocompatible
solvent and (ii) a biocompatible prepolymer and a water insoluble
contrast agent which fluid composition forms a coherent mass in the
presence of blood which mass adheres to the vascular surface and/or
the surface of the endovascular prosthesis;
[0060] (b) a catheter suitable for delivering the fluid composition
to an endoleak site formed from endovascular repair of an aneurysm;
and
[0061] (c) an endovascular prosthesis.
[0062] In a preferred embodiment, this kit further comprises a
catheter suitable for delivering an endovascular prosthesis to the
aneurysm.
DETAILED DESCRIPTION OF THE INVENTION
[0063] This invention is directed, in part, to novel methods for
sealing endoleaks in a patient which methods deliver endovascularly
a fluid composition to the site of the endoleak which composition
solidifies in situ to seal the endoleak. Specifically, the fluid
compositions used herein provide for formation of a coherent
adhesive mass which forms in situ thereby sealing endoleaks thereby
overcoming complications heretofore associated with such leaks.
[0064] However, prior to discussing this invention in further
detail, the following terms will first be defined:
[0065] The term "sealing an endoleak" refers to a process wherein a
fluid composition is injected at the site of the endoleak arising,
for example, at or adjacent the site of an abdominal aortic
aneurysm treated with an endovascular prosthesis. After delivery,
the fluid composition solidifies in situ to seal the endoleak. Any
endoleak can be treated in the methods of this invention including
endoleaks arising, for example, from incomplete sealing between the
endovascular prosthesis and the aortic wall, from defects within
the endovascular prosthesis as described below, and/or from
retrograde flow from patent lumbar and inferior mesenteric arteries
following placement of the endovascular prosthesis in the
aorta.
[0066] The term "biocompatible polymer" refers to polymers which,
in the amounts employed, are non-toxic, chemically inert, and
substantially non-immunogenic when used internally in the patient
and which, while soluble in the biocompatible solvent, are
substantially insoluble in blood. Suitable biocompatible polymers
include, by way of example, cellulose acetates.sup.7.10-11
(including cellulose diacetate.sup.9), ethylene vinyl alcohol
copolymers.sup.8,12, hydrogels (e.g., acrylics), polyacrylonitrile,
polyvinylacetate, cellulose acetate butyrate, nitrocellulose,
copolymers of urethane/carbonate, copolymers of styrene/maleic
acid, and mixtures thereof..sup.13 Preferably, the biocompatible
polymer does not induce chronic inflammation when employed in
vivo.
[0067] The particular biocompatible polymer employed is not
critical and is selected relative to the viscosity of the resulting
polymer solution, the solubility of the biocompatible polymer in
the biocompatible solvent, and the like. Such factors are well
within the skill of the art.
[0068] Preferred biocompatible polymers include cellulose diacetate
and ethylene vinyl alcohol copolymer. Cellulose diacetate polymers
are either commercially available or can be prepared by art
recognized procedures. In a preferred embodiment, the number
average molecular weight, as determined by gel permeation
chromatography, of the cellulose diacetate composition is from
about 25,000 to about 100,000 more preferably from about 50,000 to
about 75,000 and still more preferably from about 58,000 to 64,000.
The weight average molecular weight of the cellulose diacetate
composition, as determined by gel permeation chromatography, is
preferably from about 50,000 to 200,000 and more preferably from
about 100,000 to about 180,000. As is apparent to one skilled in
the art, with all other factors being equal, cellulose diacetate
polymers having a lower molecular weight will impart a lower
viscosity to the composition as compared to higher molecular weight
polymers. Accordingly, adjustment of the viscosity of the
composition can be readily achieved by mere adjustment of the
molecular weight of the polymer composition.
[0069] Ethylene vinyl alcohol copolymers comprise residues of both
ethylene and vinyl alcohol monomers. Small amounts (e.g., less than
5 mole percent) of additional monomers can be included in the
polymer structure or grafted thereon provided such additional
monomers do not alter the sealing properties of the composition.
Such additional monomers include, by way of example only, maleic
anhydride, styrene, propylene, acrylic acid, vinyl acetate and the
like.
[0070] Ethylene vinyl alcohol copolymers are either commercially
available or can be prepared by art recognized procedures.
Preferably, the ethylene vinyl alcohol copolymer composition is
selected such that a solution of 6 weight percent of the ethylene
vinyl alcohol copolymer, 35 weight percent of a tantalum contrast
agent in DMSO has a viscosity equal to or less than 60 centipoise
at 20.degree. C. As is apparent to one skilled in the art, with all
other factors being equal, copolymers having a lower molecular
weight will impart a lower viscosity to the composition as compared
to higher molecular weight copolymers. Accordingly, adjustment of
the viscosity of the composition as necessary for catheter delivery
can be readily achieved by mere adjustment of the molecular weight
of the copolymer composition.
[0071] As is also apparent, the ratio of ethylene to vinyl alcohol
in the copolymer affects the overall hydrophobicity/hydrophilicity
of the composition which, in turn, affects the relative water
solubility/insolubility of the composition as well as the rate of
precipitation of the copolymer in an aqueous solution (e.g.,
blood). In a particularly preferred embodiment, the copolymers
employed herein comprise a mole percent of ethylene of from about
25 to about 60 and a mole percent of vinyl alcohol of from about 40
to about 75. These compositions provide for requisite precipitation
rates suitable for use in sealing endoleaks arising from
endovascular repair of an abdominal aortic aneurysm.
[0072] The term "contrast agent" refers to a biocompatible
(non-toxic) radiopaque material capable of being monitored during
injection into a mammalian subject by, for example, radiography or
fluoroscopy. The contrast agent can be either water soluble or
water insoluble. Examples of water soluble contrast agents include
metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and
meglumine.
[0073] The term "water insoluble contrast agent" refers to a water
insoluble (i.e., has a water solubility of less than 0.01 mg/ml at
20.degree. C.), radiopaque material capable of being monitored
during injection into a mammalian subject by, for example,
radiography or fluoroscopy. Examples of water insoluble contrast
agents include tantalum, tantalum oxide and barium sulfate, which
are commercially available in the proper form for in vivo use.
Methods for preparing such water insoluble biocompatible contrast
agents having an average particle size of about 10 .mu.m or less
are described below. Other water insoluble contrast agents include
gold, tungsten and platinum.
[0074] The term "biocompatible solvent" refers to an organic
material liquid at least at body temperature of the mammal in which
the biocompatible polymer is soluble and, in the amounts used, is
substantially non-toxic. Suitable biocompatible solvents include,
by way of example, ethanol, acetone, dimethylsulfoxide,
analogues/homologues of dimethylsulfoxide, ethyl lactate, and the
like. Aqueous mixtures with the biocompatible solvent can also be
employed provided that the amount of water employed is sufficiently
small that the dissolved polymer precipitates upon contact with the
blood. Preferably, the biocompatible solvent is dimethylsulfoxide
(DMSO).
[0075] The term "encapsulation" as used relative to the contrast
agent being encapsulated in the polymer precipitate is not meant to
infer any physical entrapment of this agent within the precipitate
much as a capsule encapsulates a medicament. Rather, this term is
used to mean that an integral coherent precipitate forms which does
not separate into individual components.
[0076] The term "adheres to" as used herein means that the
composition formed in situ retains the position/location where the
polymer mass formed after injection and thereby functions to seal
the endoleak. This term does not necessarily infer that the
composition acts as an adhesive although in the case of, for
example, a cyanoacrylate prepolymer, the solid composition formed
may, in fact, be adhesive.
[0077] The term "biocompatible prepolymer" refers to materials
which polymerize in situ to form a polymer and which, in the
amounts employed, are non-toxic, chemically inert, and
substantially non-immunogenic when used internally in the patient
and which are substantially insoluble in blood. Suitable
biocompatible prepolymers include, by way of example,
cyanoacrylates.sup.14,15,16, hydroxyethyl methacrylate, silicone
prepolymers, and the like. The prepolymer can either be a monomer
or a reactive oligomer.sup.16. Preferably, the biocompatible
prepolymer does not induce chronic inflammation when employed in
vivo.
Compositions
[0078] The compositions used in the methods of this invention are
fluid compositions characterized by the fact that these
compositions form a coherent mass in vivo which adheres to the
vascular and/or prosthetic wall at the site of the endoleak thereby
sealing the leak. The fluid compositions employed in the methods of
this invention are polymer or prepolymer compositions prepared by
conventional methods whereby each of the components is added and
the resulting composition mixed or stirred together until the
overall composition is substantially homogeneous.
[0079] In one embodiment, fluid polymer compositions preferably
comprise a biocompatible polymer, a biocompatible solvent and
optionally a contrast agent. Such compositions can be prepared by
adding sufficient amounts of the biocompatible polymer to the
biocompatible solvent to achieve the effective concentration for
the polymer composition. Preferably, the polymer composition will
comprise from about 2.5 to about 12.0 weight percent of the
biocompatible polymer composition based on the total weight of the
polymer composition and more preferably from about 4 to about 5.4
weight percent. If necessary, gentle heating and stirring can be
used to effect dissolution of the biocompatible polymer into the
biocompatible solvent, e.g., 12 hours at 50.degree. C.
[0080] When employed, sufficient amounts of the contrast agent are
then added to the biocompatible polymer/solvent composition to
achieve the effective concentration for the complete composition.
Preferably, the composition will comprise from about 10 to about 40
weight percent of the contrast agent and more preferably from about
20 to about 40 weight percent and even more preferably about 30
weight percent. Insofar as the contrast agent may not be soluble in
the biocompatible solvent (e.g., a water insoluble contrast agent),
stirring is employed to effect homogeneity of the resulting
suspension.
[0081] In order to enhance formation of the suspension, the
particle size of the water insoluble contrast agent is preferably
maintained at about 10 .mu.m or less and more preferably at from
about 1 to about 5 .mu.m (e.g., an average size of about 2 .mu.m).
In one preferred embodiment, the appropriate particle size of the
contrast agent is prepared, for example, by fractionation. In such
an embodiment, a water insoluble contrast agent such as tantalum
having an average particle size of less than about 20 microns is
added to an organic liquid such as ethanol (absolute) preferably in
a clean environment. Agitation of the resulting suspension followed
by settling for approximately 40 seconds permits the larger
particles to settle faster. Removal of the upper portion of the
organic liquid followed by separation of the liquid from the
particles results in a reduction of the particle size which is
confirmed under an optical microscope. The process is optionally
repeated until a desired average particle size is reached.
[0082] When no contrast agent is employed, the biocompatible
solvent is preferably employed at a concentration of from 88 to
about 97.5 weight percent of the biocompatible polymer composition
based on the total weight of the polymer composition and more
preferably from about 90 to about 95 weight percent.
[0083] When a contrast agent is employed, the biocompatible solvent
is preferably employed at a concentration of from 52 to 87.5 weight
percent based on the total weight of the composition; more
preferably from about 54.8 to about 76 weight percent; and even
more preferably 64.8 to about 66 weight percent. Typical examples
of suitable concentrations of individual components are given in
the table below:
1 Example Polymer Solvent Contrast Agent A 2.5 weight % 97.5 weight
% -- B 8 weight % 92 weight % -- C 2.5 weight % 87.5 weight % 10
weight % D 8 weight % 82 weight % 10 weight % E 2.5 weight % 57.5
weight % 40 weight % F 8 weight % 52 weight % 40 weight % G 8
weight % 72 weight % 20 weight % H 2.5 weight % 67.5 weight % 30
weight % I 8 weight % 62 weight % 30 weight % J 4 weight % 66
weight % 30 weight % K 5.4 weight % 64.6 weight % 30 weight %
[0084] The particular order of addition of components to the
biocompatible solvent is not critical and stirring of the resulting
solution/suspension is conducted as necessary to achieve
homogeneity of the composition. Preferably, mixing/stirring of the
composition is conducted under an anhydrous atmosphere at ambient
pressure. The resulting composition is heat sterilized and then
stored preferably in sealed amber bottles or vials until
needed.
[0085] Each of the polymers recited herein is commercially
available but can also be prepared by methods well known in the
art. For example, polymers are typically prepared by conventional
techniques such as radical, thermal, UV, .gamma. irradiation, or
electron beam induced polymerization employing, as necessary, a
polymerization catalyst or polymerization initiator to provide for
the polymer composition. The specific manner of polymerization is
not critical and the polymerization techniques employed do not form
a part of this invention.
[0086] In order to maintain solubility in the biocompatible
solvent, the polymers described herein are preferably not
cross-linked.
[0087] In another embodiment, the fluid compositions comprise
prepolymer compositions which preferably comprise a biocompatible
prepolymer and a water insoluble contrast agent. Such compositions
can be prepared by adding sufficient amounts of the contrast agent
to the solution (e.g., liquid prepolymer) to achieve the effective
concentration for the complete composition. Preferably, the
prepolymer composition will comprise from about 10 to about 40
weight percent of the contrast agent and more preferably from about
20 to about 40 weight percent and even more preferably about 30
weight percent. The water insoluble contrast agent is typically not
soluble in the biocompatible prepolymer composition and stirring is
employed to effect homogeneity of the resulting suspension. In
order to enhance formation of the suspension, the particle size of
the contrast agent is preferably maintained at about 10 .mu.m or
less and more preferably at from about 1 to about 5 .mu.m (e.g., an
average size of about 2 .mu.m).
[0088] When the prepolymer is liquid, the use of a biocompatible
solvent is not absolutely necessary but may be preferred to provide
for an appropriate viscosity, etc. in the composition. Preferably,
when employed, the biocompatible solvent will comprise from about
30 to about 90 weight percent of the biocompatible prepolymer
composition based on the total weight of the prepolymer composition
and more preferably from about 60 to about 80 weight percent. When
a biocompatible solvent is employed, the prepolymeric composition
typically comprises from about 10 to about 50 weight percent of the
prepolymer based on the total weight of the composition. Typical
examples of suitable concentrations of individual components are
given in the table below:
2 Example Prepolymer Solvent Contrast Agent L 90 weight % -- 10
weight % M 85 weight % -- 15 weight % N 80 weight % -- 20 weight %
O 70 weight % -- 30 weight % P 60 weight % -- 40 weight % Q 50
weight % 30 weight % 20 weight % R 10 weight % 80 weight % 10
weight % S 40 weight % 30 weight % 40 weight % T 50 weight % 40
weight % 10 weight % U 40 weight % 40 weight % 30 weight % V 30
weight % 30 weight % 40 weight %
[0089] In a particularly preferred embodiment, the prepolymer is a
cyanoacrylate ester which is preferably employed in the absence of
a biocompatible solvent. When so employed, the cyanoacrylate
composition is selected to have a viscosity of from about 5 to
about 20 centipoise at 20.degree. C.
[0090] The particular order of addition of components is not
critical and stirring of the resulting suspension is conducted as
necessary to achieve homogeneity of the composition. Preferably,
mixing/stirring of the composition is conducted under an anhydrous
atmosphere at ambient pressure. The resulting composition is
sterilized and then stored preferably in sealed amber bottles or
vials until needed.
Methods
[0091] The compositions described above can then be employed in
methods for the catheter assisted sealing of endoleaks formed by
endovascular repair of an abdominal aortic aneurysm by an
endovascular prosthesis.
[0092] Specifically, endovascular repair of such aneurysms involves
the introduction of an endovascular prosthesis into the abdominal
aortic aneurysm which is an art recognized procedure described, for
example, by Parodi..sup.17 This procedure typically consists of
dissection of the femoral artery at the groin and introduction of
an endovascular prosthesis inside the abdominal aortic aneurysm.
Upon insertion, the prosthesis excludes the aneurysm sac from the
systemic vascular circulation thereby repairing the aneurysm.
Suitable endovascular prostheses for endovascular repair of
abdominal aortic aneurysms are well known in the art and are
described, for example, by Beebe, et al..sup.5 Such prostheses, by
themselves, do not form part of this invention. Similarly,
catheters for delivering such endovascular prostheses to the site
of the abdominal aortic aneurysm are also well known in the art and
are commercially available. Such catheters, by themselves, also do
not form part of this invention.
[0093] In any event, in the methods of this invention, a sufficient
amount of the fluid composition described above is introduced at
the site of the endoleak via a catheter or needle delivery means
preferably under fluoroscopy so that sealing of the endoleak can be
visualized. The specific amount of fluid composition employed is
dictated by the total size of the endoleak, whether penetration of
the fluid composition into the aneurysm is desirable and/or
achievable and other factors such as the concentration of
polymer/prepolymer in the composition, the rate of solids
formation, etc. Such factors are well within the skill of the
art.
[0094] Prior to sealing the endoleak in the manner described above,
the clinician would first identify the site or sites of the
endoleak which typically include the interface of the aortic wall
to the end of the endovascular prosthesis; defects within the
endovascular prosthesis such as at juncture points between segments
of the prosthesis which permit blood flow through the prosthesis
itself; and retrograde flow from patent lumbar and inferior
mesenteric arteries following placement of the endovascular
prosthesis in the aorta.
[0095] Access to these sites of endoleaks can be achieved by
microcatheter retrograde access via the patent lumbar and/or
inferior mesenteric arteries or by endovascular methods or
percutaneous puncture at the site of the endoleak. After access is
achieved, delivery of the fluid composition proceeds as described
above.
[0096] One particularly preferred method for catheter delivering
the compositions described in the methods of this invention to the
site of the endoleak is via a small diameter medical catheter. The
particular catheter employed is not critical provided that
polymeric catheter components are compatible with the fluid
composition (i.e., the catheter components will not readily degrade
in the fluid composition). In this regard, it is preferred to use
polyethylene in the catheter components because of its inertness in
the presence of the fluid composition described herein. Other
materials compatible with the fluid compositions can be readily
determined by the skilled artisan and include, for example, other
polyolefins, fluoropolymers (e.g., Teflon.TM.), silicone, etc.
[0097] Another particularly preferred method for the catheter
injection of the polymer composition of this invention is described
by Greff, et al., U.S. Pat. No. 5,830,178 which issued on Nov. 3,
1998 and which is incorporated herein by reference in its
entirety.
[0098] When a fluid composition comprising a biocompatible polymer
is introduced at the site of the endoleak, the biocompatible
solvent diffuses rapidly into the blood and a solid coherent mass
forms in situ which precipitate is the water insoluble polymer with
any contrast agent encapsulated therein. Without being limited to
any theory, it is believed that initially, a soft gel to spongy
solid precipitate forms upon contact with the blood which mass
adheres to the vascular or prosthetic wall thereby sealing the
endoleak.
[0099] When a fluid composition comprising a biocompatible
prepolymer is introduced at the site of the endoleak, the
prepolymer polymerizes in situ to form a solid coherent mass or
film with any water insoluble contrast agent encapsulated therein.
This mass adheres to the vascular and/or prosthetic wall thereby
sealing the endoleak.
[0100] When a contrast agent is employed in the fluid composition,
sealing of the endoleak by this composition can be confirmed by
injection of an independent contrast agent such iopamidol (50:50
mixture with saline) into the blood flow of the aorta. Failure of
this contrast agent to reach the aneurysm sac as visualized by
fluoroscopy confirms sealing of the endoleak.
[0101] The sealing of endoleaks can be conducted during the
surgical repair of the abdominal aortic aneurysm or in a separate
surgical procedure conducted subsequent to the surgical repair. All
that is required is the determination of the location of the
endoleaks in the patient and introduction of the fluid composition
to seal such endoleaks.
[0102] The methods of this invention are preferably conducted by
using kits of parts comprising two or more of the components
necessary to effect the endoleak repair protocol. For example, in
one embodiment, this kit comprises the following components:
[0103] (a) a fluid composition comprising a composition selected
from the group consisting of (i) a biocompatible polymer and a
biocompatible solvent and (ii) a biocompatible prepolymer and a
water insoluble contrast agent which fluid composition forms a
coherent mass in the presence of blood which mass adheres to the
vascular surface and/or the surface of the endovascular
prosthesis;
[0104] (b) a catheter suitable for delivering the fluid composition
to an endoleak site formed from endovascular repair of an aneurysm;
and
[0105] (c) a catheter suitable for delivering an endovascular
prosthesis to the aneurysm.
[0106] In a preferred embodiment, this kit further comprises an
endovascular prosthesis.
[0107] In another embodiment, this kit comprises the following
components:
[0108] (a) a fluid composition comprising a composition selected
from the group consisting of (i) a biocompatible polymer and a
biocompatible solvent and (ii) a biocompatible prepolymer and a
water insoluble contrast agent which fluid composition forms a
coherent mass in the presence of blood which mass adheres to the
vascular surface and/or the surface of the endovascular
prosthesis;
[0109] (b) a catheter suitable for delivering the fluid composition
to an endoleak site formed from endovascular repair of an aneurysm;
and
[0110] (c) an endovascular prosthesis.
[0111] In a preferred embodiment, this kit further comprises a
catheter suitable for delivering an endovascular prosthesis to the
aneurysm.
Utility
[0112] The methods described herein are useful in reducing or
eliminating blood flow through an endoleak into an endovascularly
repaired aneurysm thereby reducing or eliminating the possible
rupture of the aneurysm. Accordingly, these methods find use in
human and other mammalian subjects requiring closure of such
endoleaks. Additionally, when a water insoluble contrast agent is
employed, the stability of the closure can be monitored weeks,
months or even years after sealing by non-invasive fluoroscopic
techniques. Resealing of the endoleak is also facilitated by the
presence of the water insoluble contrast agent which permits the
clinician to readily identify the site of treated endoleaks.
[0113] It is contemplated that the procedures set forth above can
be employed for sealing endoleaks arising from insertion of an
endovascular prosthesis at vascular sites other than the abdominal
aorta. Such prostheses could be used to repair aneurysms and other
vascular diseases at vascular sites such as peripheral vessels.
[0114] The following examples are set forth to illustrate the
claimed invention and are not to be construed as a limitation
thereof.
EXAMPLES
[0115] Unless otherwise stated, all temperatures are in degrees
Celsius. Also, in these examples and elsewhere, the following
abbreviations have the following meanings:
3 atm atmospheres cc cubic centimeter cm centimeter DMSO
dimethylsulfoxide EVOH ethylene vinyl alcohol copolymer g gram hrs
hours IM intramuscularly in. inch IU international units IV
intravenously kg kilogram mg milligram min. minute mL milliliter mm
millimeter PTFE polytetrafluoroethylene sec. seconds SQ
subcutaneously .mu.m micron
Example 1
[0116] The purpose of this example is to demonstrate the
preparation of a fluid polymer composition useful in the methods of
this invention.
[0117] Specifically, an EVOH polymer composition was prepared as
follows:
Composition
[0118] A) 8 g EVOH;
[0119] B) 30 g tantalum having an average particle size of about 3
.mu.m (narrow size distribution); and
[0120] C) 100 mL DMSO.
[0121] Component A) was added to Component C) at 50.degree. C. and
stirred for 2 hrs on a hot plate under an argon blanket. To this
resulting composition was added Component B and the resulting
mixture was mixed until homogeneous.
Example 2
[0122] This example illustrates sealing of endoleaks arising from
endo-vascular repair of an abdominal aortic aneurysm in a dog
model. The following illustrates the protocol employed:
Equipment Used
[0123] 0.035/0.038 3J Guide Wires (Cook, Bloomington, Ind.)
[0124] 10-14F Introducer Sheaths (Daig, Minnetonka, Minn.)
[0125] Angioplasty Balloon Catheters
(10.times.2/10.times.4/10.times.6/16.- times.2/16.times.4
18.times.2/18.times.4)-(Blue Max and XXL; Meditech, Mass.)
[0126] 4 mm Aortic Punch (Medtronic, Minneapolis, Minn.)
[0127] Palmaz Stents: P4014, P5014 (Johnson and Johnson
Interventional Systems, New Jersey)
[0128] Infusion Catheters (Easy Rider.TM. 3F, Micro Therapeutics,
Irvine, Calif.)
[0129] Microguide Wire (Silver Speed.TM., Micro Therapeutics,
Irvine, Calif.)
[0130] Composition of Example 1
[0131] Contrast Media-Hypaque-76.TM. (Nycomed, Princeton, N.J.)
[0132] 7 and 8F Guiding Catheters (Medtronics, Minneapolis,
Minn.)
[0133] 10 mm and 12 mm diameter polyethylene terephthalate
Wallgrafts.TM. (Schneider, Boston Scientific, Natick, Mass.)
[0134] 5F Angiographic Catheters (Cordis, Miami Lakes, Fla.)
Pre-surgical Procedures
[0135] The animal was fasted 24 hrs prior to surgery and then
pre-anesthetized with 0.01 mg/kg Glycopyrrolate SQ followed by
anesthetization with a combination of Butorphanol, Xylazine, and
Telazol. This combination was given such that 6.6/kg Telazol is
given IM. Next, the animal was intubated and connected to
Isoflurane gas anesthesia of 1-3%.
[0136] A 20 gauge catheter was placed into the cephalic vein of the
animal and 0.9% saline was administered intravenously at a rate of
1-4 mL/kg/hr and then 15 mL blood was collected for CBC liver
profile.
[0137] A standard sterile surgical preparation and draping was
utilized. The carotid or femoral artery was exposed via vessel
cutdown and distal and proximal hemostatic loops placed. An
arteriotomy was then performed and the introducer sheath (10-14F)
was advanced into the artery lumen. The sheath and artery was then
secured.
[0138] After the introducer was placed, the animal was IV
heparinized with 100 units of heparin/kg of body weight.
[0139] A 7-8 F guiding catheter was introduced over a standard
0.035 inch, 3 mm "J" guide wire. A flush anteroposterior projection
aortogram was obtained with use of contrast media, and the
mediolateral diameter of the dog infrarenal aorta was measured with
the use of the markers on the pigtail as standardization. A flat
film X-ray was required during the contrast arteriography.
[0140] In accordance of the measurements of the infrarenal aorta, a
Palmaz stent was deployed into the infrarenal aorta on a 10-16 mm
diameter, 4 cm long angioplasty balloon with use of fluoroscopic
guidance. Then the infrarenal aortic stent was overdilated to
1.5-2.0 its measured normal diameter in the dog at 6-8 atm using a
standard pressure gauge for a single inflation lasting 30 sec.
[0141] The balloon was removed over a wire and replaced with the
measuring pigtail catheter. A repeat aortogram was obtained and the
abdominal aortic aneurysm was measured in the animal. A flat film
with and without contrast media injections was obtained with all
prostheses in the field of view.
[0142] A Wallgraft was then inserted with the model AAA. Each
Wallgraft was medially perforated with a 4 mm aortic punch which
produced a graft defect that was the source of the endoleak. These
endografts were placed coaxially within the aneurysms.
[0143] A repeat aortogram was obtained. A flat film with and
without contrast media injections was obtained with all prostheses
in the field of view.
[0144] Upon completion, the arteriotomy was closed with interrupted
polypropylene sutures and the surrounding tissue Were sutured. The
animal was allowed to recover before being returned to a cage.
[0145] At the conclusion of surgery, the animal was given
approximately 25,000 IU/kg procaine and benzathine penicillin
SQ.
[0146] Post-operatively, the animal received 325 mg/day of aspirin
for 6 weeks and ampicillin 1 g/day for 3 days.
Endoleak Treatment
[0147] After 1 week, a CT-scan with and without contrast media was
performed on the dog. A major leak at the graft defect (4 mm hole)
that involved flow through a number of lumbar arteries and the
distal stent graft to the aortic wall interface seal was noted. The
animal was returned to a second phase of the study.
[0148] Treatment of the endoleaks was performed immediately after
the CT scan. The animal had been fasted 24 hours prior to surgery
and then pre-anesthetized with 0.01 mg/kg Glycopyrrolate SQ
followed by anesthetization with a combination of Butorphanol,
Xylazine, and Telazol. This combination was given such that 6.6
mg/kg Telazol is given IM. Next, the animal was intubated and
connected to Isoflurane gas anesthesia of 1-3%.
[0149] A 20 gauge catheter was placed into the cephalic vein of the
animal and 0.9% saline was administered intravenously at a rate of
1-4 mL/kg/hr.
[0150] A standard sterile surgical preparation and draping was
utilized. The carotid or femoral artery was exposed via vessel
cutdown and distal and proximal hemostatic loops placed. An
arteriotomy was then performed and the introducer sheath (10-12F)
was advanced into the carotid artery lumen. The sheath and artery
were then secured.
[0151] After the introducer has been placed, the animal was IV
heparinized with 100 units of heparin/kg of body weight.
[0152] A 7-8 F guiding catheter was introduced over a standard
0.035 inch, 3 mm J guide wire. A flush anteroposterior projection
aortogram was obtained with the use of contrast media. The
endoleaks were observed. A flat film X-ray with and without
contrast media injections was obtained with the aneurysm in the
field of view.
[0153] The guiding catheter was removed and a 5F guiding catheter
was placed adjacent to the 4 mm "hole". A small amount of contrast
was given to confirm the position of the endoleak.
[0154] A microguide wire (0.010 inch) was passed through 5 F
catheter and through the endograft hole. An infusion microcatheter
was positioned over the wire and inside the aneurysm sac and about
1 cc of the fluid composition of Example 1 was administered under
fluoroscopy until complete seal of the endoleak was achieved with
filling of the lumber arteries and around the cuff or interface of
the stent graft to the aortic wall. Contrast injection confirmed no
blood flow through this endoleak pathway. Flat films were taken to
document the results.
[0155] Follow-up aortography and CT scan was performed 5 weeks
later, confirming successful treatment of the endoleaks. The above
data demonstrates that the methods of this invention effectively
seal endoleaks in vivo.
Example 3
[0156] This example illustrates the procedures used to access a
simulated endoleak within the aneurysm sac after placement of the
prosthesis within the AAA. Specifically, this example employs the
following protocol.
[0157] A 25 kg male dog was prepared and anesthetized per Example 2
above. An abdominal midline incision was then made and the
descending aorta exposed. A 15 mm arteriotomy was made in the aorta
and a patch of fascia was sutured onto this opening creating an
aneurysm of a size of about 4.5.times.3.5.times.4.0 cm. Three 4F
Fogarty balloon catheters were placed into the aneursym via the
carotid artery under fluoroscopy and each balloon catheter was then
filled with contrast solution comprising 1:1 saline:Hypaque 76
(0.25 cc, 0.25 cc and 0.5 cc respectively). A 12 mm.times.5 cm Wall
stent graft was placed within the aorta and over the aneurysm
opening. To access the aneurysm sac through the graft, a 6 F guide
catheter was placed into the aorta to the graft via the femoral
artery and a 22 G.times.40 cm needle introduced through the guide
catheter. The needle tip was bent about 45 degrees. Under
fluoroscopy, the graft wall was punctured and the needle tip
advanced into the aneurysm sac. Each of the three filled balloons
was successfully located and punctured to release the contrast
agent which was visualized via fluoroscopy. To complete this
simulation, a sufficient amount of the composition of Example 1 was
then injected through the needle to fill the aneurysm sac. This
composition, upon contact with the blood in the aneurysm sac
solidified.
[0158] From the foregoing description, various modifications and
changes in the above described methods will occur to those skilled
in the art. All such modifications coming within the scope of the
appended claims are intended to be included therein.
* * * * *