U.S. patent number RE31,035 [Application Number 05/922,654] was granted by the patent office on 1982-09-21 for arrangement for preparing natural tissue for implantation.
This patent grant is currently assigned to Hancock Laboratories, Inc.. Invention is credited to Warren D. Hancock, Frederick P. Sattler.
United States Patent |
RE31,035 |
Hancock , et al. |
September 21, 1982 |
Arrangement for preparing natural tissue for implantation
Abstract
An arrangement for preparing natural tissue in the form of a
heart valve, vessel or the like for implantation in which tanning
fluid under pressure is applied to a portion of the tissue so as to
cause said tissue to assume substantially its natural
configuration, while additional tanning fluid is applied to the
remainder of the tissue, said tanning fluid being so applied for a
time sufficient to cause the tissue to become fixed, and, for
vessels or the like, a guide may engage the tissue during fixation,
whereby said tissue maintains substantially the configuration of
the guide.
Inventors: |
Hancock; Warren D. (Newport
Beach, CA), Sattler; Frederick P. (Fullerton, CA) |
Assignee: |
Hancock Laboratories, Inc.
(Anaheim, CA)
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Family
ID: |
27413875 |
Appl.
No.: |
05/922,654 |
Filed: |
July 7, 1978 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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490686 |
Jul 22, 1974 |
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324217 |
Jan 16, 1973 |
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28630 |
Apr 15, 1970 |
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Reissue of: |
665520 |
Mar 10, 1976 |
04050893 |
Sep 27, 1977 |
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Current U.S.
Class: |
8/94.11; 600/36;
623/26; 623/921 |
Current CPC
Class: |
A61F
2/2415 (20130101); A61F 2/062 (20130101) |
Current International
Class: |
A61F
2/06 (20060101); A61F 2/24 (20060101); C14C
003/16 () |
Field of
Search: |
;8/94.11 |
References Cited
[Referenced By]
U.S. Patent Documents
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2900644 |
August 1959 |
Rosenberg et al. |
3966401 |
June 1976 |
Hancock et al. |
3988782 |
November 1976 |
Dardick et al. |
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Foreign Patent Documents
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1938275 |
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Oct 1970 |
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DE |
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2241698 |
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Mar 1973 |
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DE |
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2077641 |
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May 1971 |
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FR |
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2064151 |
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Jul 1971 |
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FR |
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2151092 |
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Apr 1973 |
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FR |
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1325667 |
|
Aug 1973 |
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GB |
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Other References
Carpentier, "J. Thoracic & Cardiovascular Surgery", vol. 58,
No. 4, Oct. 1969, pp. 467-483. .
Reed, "J. Thoracic & Cardiovascular Surgery, " vol. 57, No. 5,
May 1969, pp. 663-668. .
Weldon, "A Prosthetic Stented Aortic Homograft for Mitral Valve
Replacement", J. of Surgical Research, vol. 6, No. 12, Dec. 1966,
pp. 548-552. .
Eckner, "Virchows Arch. Abt. A. Path. Anat.", 346, pp. 318-329,
1969. .
Glagov, "Archives of Pathology", vol. 76, Dec. 1963, pp. 62-68.
.
Wood, "J. Thoracic & Cardiovascular Surgery", vol. 46, No. 3,
Sep. 1963, pp. 379-385. .
Rosenberg, "Surgical Forum", vol. 6, 1955, pp. 242-246. .
Creech, "Surgery", Sep. 1954, pp. 431-444. .
Peirce, "American J. of Surgery", Sep. 1949, pp. 314-323. .
Wolinsky, "Circulation Research", vol. XIV, May 1964, pp. 400-413.
.
Braunwald et al., vol. XIII, Trans. Amer. Society of Artificial
Organs, 1967, pp. 111-113. .
Geha et al., J of Thoracic and Cardiovascular Surgery, vol. 54, No.
5, Nov. 1967, pp. 605-629..
|
Primary Examiner: Michl; Paul R.
Attorney, Agent or Firm: Gausewitz, Carr, Rothenberg &
Edwards
Parent Case Text
REFERENCE TO RELATED APPLICATIONS
This is a continuation of patent application Ser. No. 490,686,
filed July 22, 1974, now abandoned which is a continuation-in-part
of our application Ser. No. 324,217 filed Jan. 16, 1973, now
abandoned, which was a continuation of patent application Ser. No.
28,630, filed Apr. 15, 1970, now abandoned.
Claims
We claim:
1. The method of preparing .Iadd.a .Iaddend.natural heart valve for
implantation .Iadd.so that said valve will have improved tensile
strength, will have and retain a generally regular contour with the
cusps thereof closed as in diastole, and will be in substantially
its natural configuration, so that said valve will remain competent
for a prolonged period upon implantation, .Iaddend.comprising the
steps of
.Iadd.excising a heart valve from a donor heart, .Iaddend.applying
a tanning fluid under pressure in the physiologic range to the
downstream end of .[.a natural.]. .Iadd.said .Iaddend.heart valve
.Iadd.so excised .Iaddend.so as to cause said valve to assume
.Iadd.a generally regular contour with the cusps thereof coapted
and closed as in diastole so that said valve is in
.Iaddend.substantially its natural configuration,
and simultaneously applying a tanning fluid to the upstream end of
said valve .Iadd.and to substantially the entire exterior surface
of said valve .Iaddend.at a pressure less than that at said
downstream end,
thereby to cause said valve substantially to maintain said
configuration during .Iadd.and after .Iaddend.fixation of the
tissue thereof .Iadd.so that said valve can remain competent for a
prolonged period of use upon implantation. .Iaddend.
2. The method of preparing .[.a.]. .Iadd.the .Iaddend.natural heart
valve .Iadd.of an animal .Iaddend.for implantation .Iadd.in a
patient so that said valve will have improved tensile strength,
will have and retain a generally regular contour with the cusps
thereof closed as in diastole, and will be in substantially its
natural configuration, so that said valve will remain competent for
a prolonged period of use upon implantation .Iaddend.comprising the
steps of
.Iadd.excising a heart valve from an animal heart,
.Iaddend.applying a tanning fluid under pressure within the
physiologic range to the downstream end of .[.a natural.].
.Iadd.said .Iaddend.heart valve .Iadd.so excised .Iaddend.so as to
cause said valve to assume .Iadd.a generally regular contour with
the cusps thereof coapted and closed as in diastole so that said
valve is in .Iaddend.substantially its natural configuration,
applying said tanning fluid to the upstream end of said valve while
said tanning fluid under pressure is so applied to said valve at
the downstream end thereof so that said valve is at a higher
pressure .Iadd.from said tanning fluid .Iaddend.at said downstream
end than at said upstream end,
.[.and.]. maintaining said tanning fluid so applied to said heart
valve for a time sufficient to cause said valve to become fixed so
as to substantially maintain said configuration .Iadd.and to have
improved tensile strength, whereby said valve can remain competent
for a prolonged period of use upon implantation, and thereafter
removing said valve so fixed from said tanning fluid and mounting
said valve on a stent for subsequent implantation. .Iaddend.
3. The method as recited in claim 2 in which said pressure is
substantially within the range of from about 80 to about 120 mm
Hg.
4. The method as recited in claim 2 in which said tanning fluid is
a 4% formaldehyde solution, and in which said tanning fluid is so
applied to said valve for around 72 hours.
5. The method as recited in claim 2 in which said tanning fluid is
a 0.2% glutaraldehyde solution, and in which said tanning fluid is
so applied to said valve for around 72 hours.
6. The method as recited in claim 2 in which said tanning fluid
under pressure is applied to said valve by maintaining a quantity
of said tanning fluid so as to have a predetermined maximum height
with respect to said valve, and connecting said quantity of tanning
fluid to said valve so that said quantity of tanning fluid produces
a pressure head applied to said valve.
7. The method of preparing a natural heart valve for implantation
.Iadd.so that said valve will have improved tensile strength, will
have and retain a generally regular contour with the cusps thereof
closed as in diastole, and will be in substantially its natural
configuration, so that said valve will remain competent for a
prolonged period upon implantation, .Iaddend.comprising the steps
of
.Iadd.excising from a donor heart a unit that includes a heart
valve and its ascending aorta, then .Iaddend.inserting .Iadd.into
said ascending aorta above said heart valve .Iaddend.a member
having an aperture therethrough.Iadd., .Iaddend..[.into the
ascending aorta of a unit that includes a natural heart valve and
its ascending aorta,.].
attaching said aorta to said member so that said unit and said
member define a chamber .Iadd.closed at one end by the cusps of
said heart valve .Iaddend.and said aperture provides access to the
interior of said chamber at the downstream end of said valve,
ligating the arteries of said unit so as to close said chamber,
introducing a tanning fluid which is pressurized to within the
physiologic range of pressure for said valve through said aperture
into said chamber so as to inflate said valve and cause said valve
to assume .Iadd.a generally regular contour with the cusps thereof
coapted and closed as in diastole so that said valve is
.Iaddend.substantially its natural configuration, .Iadd.with said
tanning fluid being retained by said cusps of said heart valve,
.Iaddend.
applying such tanning fluid to the exterior of said unit .Iadd.so
that said tanning fluid engages substantially the entire exterior
surface of said heart valve .Iaddend.while said pressurized tanning
fluid is in said chamber with a greater fluid pressure existing in
said chamber than on said exterior,
.[.and.]. maintaining said pressurized tanning fluid and said
tanning fluid so applied to the exterior of said unit for a time
sufficient to cause the tissue of said valve to become
substantially fixed,
thereby to cause said valve to substantially maintain said
configuration .Iadd.and to have improved tensile strength, and
thereafter removing said valve so fixed from said tanning fluid and
mounting said valve on a stent in preparation for implantation.
.Iaddend.
8. The method as recited in claim 7 in which for introducing said
pressurized fluid into said chamber a source of said tanning fluid
is maintained at a predetermined height relative to said unit, and
in which a conduit is extended from said source of said tanning
fluid to said chamber to cause said tanning fluid at said source to
provide a predetermined pressure head.
9. The method as recited in claim 8 in which said predetermined
height is selected so as to provide a pressure head of around 80 mm
Hg. .[.10. The method of preparing for implantation natural tissues
in a form in which a portion thereof is subjected to pressure
within the physiologic range when implanted and which assumes a
predetermined configuration as a result of such pressure comprising
the steps of
applying a tanning fluid to said portion of said tissues,
said tanning fluid so applied being under pressure in the
physiologic range so as to cause said tissues to assume
substantially said predetermined configuration,
and simultaneously applying a tanning fluid to remaining parts of
said tissues at a pressure less than that of said portion of said
tissues,
thereby to cause said tissues to assume said configuration during
fixation of said tissues..]. .[.11. The method as recited in claim
10 in which, for so applying said tanning fluid to said portion of
said tissues with said tanning fluid being under pressure within
the physiologic range, a source of said tanning fluid under
pressure is provided, and a conduit is extended from said source to
said portion of said tissues, for thereby so applying said tanning
fluid to said portion of said tissues..]. .[.12. The method as
recited in claim 11 in which, for said source of said tanning fluid
under pressure, a quantity of said tanning fluid is provided at a
predetermined height relative to said portion of said tissues..].
.[.13. The method of preparing a vessel for implantation comprising
the steps of
subjecting said vessel to a bath of tanning fluid so as to fix said
vessel,
and simultaneously engaging said vessel with a guide member of
predetermined contour for causing said vessel to assume
substantially said predetermined contour upon fixation thereof,
said predetermined contour being different from the contour of said
vessel in its natural state..]. .[.14. The method of preparing for
implantation natural tissues in a form in which a portion thereof
is subjected to pressure within the physiologic range when
implanted and which assumes a predetermined configuration as a
result of such pressure comprising the steps of
applying a tanning fluid to said portion of said tissues, said
tanning fluid so applied being under pressure within the
physiologic range so as to cause said tissues to assume
substantially said predetermined configuration,
and applying a tanning fluid to remaining parts of said tissues
while said tanning fluid under pressure is so applied to said
portion of said tissues,
so that said tissues experience a higher pressure at said portion
thereof than at said remaining parts thereof..]. .[.15. The method
as recited in claim 14 including the step of engaging said tissues
with a guide member of predetermined contour while said tanning
fluid under pressure within the physiologic range is so applied to
said portion of said tissues for causing said tissues to assume
substantially said predetermined contour..]. .[.16. The method as
recited in claim 15 in which said tissues constitute a vessel..].
.[.17. The method as recited in claim 16 in which said vessel in
its natural state has substantially said predetermined contour..].
.[.18. The method as recited in claim 16 in which said vessel in
its natural state has a contour different from said predetermined
contour..]. .[.19. The method as recited in claim 28 in which said
predetermined contour is substantially U-shaped..]. .[.20. The
method as recited in claim 16 in which, for said engaging of said
vessel with a guide member, an elongated element having
substantially said predetermined contour, and a lateral dimension
less than that assumed by said vessel when subjected to pressure
within the physiologic range, is inserted into said vessel for
thereby maintaining said vessel substantially in said predetermined
contour..]. .[.21. The method as recited in claim 16 in which, for
said engaging of said vessel with a guide member, said vessel is
placed within a tubular element having substantially said
predetermined contour and an interior lateral dimension
approximately that assumed by said vessel when subjected to
pressure within the physiologic range, for thereby maintaining said
vessel substantially in said predetermined contour..]. .[.22. The
method as recited in claim 16 in which, for applying said pressure
to said vessel, the end and any collaterals thereof are ligated,
and said tanning fluid under pressure within said physiologic range
is introduced into the interior of said vessel..]. .[.23. The
method as recited in claim 22 in which, for introducing said
tanning fluid under pressure within the physiologic range into said
vessel, a source of said tanning fluid is maintained at a
predetermined hight relative to said vessel, and a conduit is
extended from said source of said tanning fluid to said vessel to
cause said tanning fluid at said source to provide a
predetermined pressure head..]. 24. A .Iadd.stent-mounted
.Iaddend.natural heart valve for implantation having a generally
regular contour, natural shape and size, coaptation of the cusps
thereof and relatively high tensile strength prepared by the steps
of
.Iadd.excising a heart valve from a donor heart, .Iaddend.applying
a tanning fluid under pressure in the physiologic range to the
downstream end of .[.a natural.]. .Iadd.said .Iaddend.heart valve
.Iadd.so excised .Iaddend.so as to cause said valve to assume
substantially its natural configuration, and simultaneously
applying a tanning fluid to the upstream end of said valve
.Iadd.and to substantially the entire exterior surface of said
valve .Iaddend.at a pressure less than that at said downstream
end,
thereby to cause said valve substantially to maintain said
configuration
during fixation of the tissue thereof. 25. A .Iadd.stent-mounted
.Iaddend.natural heart valve for implantation having a generally
regular contour, natural shape and size, coaptation of the cusps
thereof and relatively high tensile strength prepared by the steps
of
.Iadd.excising a heart valve from an animal heart,
.Iaddend.applying a tanning fluid under pressure within the
physiologic range to the downstream end of .[.a natural.].
.Iadd.said .Iaddend.heart valve .Iadd.so excised .Iaddend.so as to
cause said valve to assume substantially its natural
configuration,
applying said tanning fluid to the upstream end of said valve
.Iadd.so that said tanning fluid engages substantially the entire
exterior surface of said valve .Iaddend.while said tanning fluid
under pressure is so applied to said valve at the downstream end
thereof so that said valve is at a higher pressure .Iadd.from said
tanning fluid .Iaddend.at said downstream end than at said upstream
end,
and maintaining said tanning fluid so applied to said heart valve
for a time sufficient to cause said valve to become fixed so as to
substantially
maintain said configuration. 26. The heart valve as recited in
claim 25 in which said pressure is substantially within the range
of from about 80 to
about 120 mm Hg. 27. The heart valve as recited in claim 25 in
which said tanning fluid is a 4% formaldehyde solution, and in
which said tanning
fluid is so applied to said valve for around 72 hours. 28. The
heart valve as recited in claim 25 in which said tanning fluid is a
0.2% glutaraldehyde solution, and in which said tanning fluid is so
applied to
said valve for around 72 hours. 29. The heart valve as recited in
claim 25 in which said tanning fluid under pressure is applied to
said valve by maintaining a quantity of said tanning fluid so as to
have a predetermined maximum height with respect to said valve, and
connecting said quantity of tanning fluid to said valve so that
said quantity of tanning fluid
produces a pressure head applied to said valve. 30. A
.Iadd.stent-mounted .Iaddend.natural heart valve for implantation
having a generally regular contour, natural shape and size,
coaptation of the cusps thereof and relatively high tensile
strength prepared by the steps of
.Iadd.excising from a donor heart a unit that includes a heart
valve and its ascending aorta, then .Iaddend.inserting .Iadd.into
said ascending aorta above said heart valve .Iaddend.a member
having an aperture therethrough.Iadd., .Iaddend. .[.into the
ascending aorta of a unit that includes a natural heart valve and
its ascending aorta,.].
attaching said aorta to said member so that said unit and said
member define a chamber .Iadd.closed at one end by the cusps of
said heart valve .Iaddend.and said aperture provides access to the
interior of said chamber at the downstream end of said valve,
ligating the arteries of said unit so as to close said chamber,
introducing a tanning fluid which is pressurized to within the
physiologic range of pressure for said valve through said aperture
into said chamber so as to inflate said valve and cause said valve
to assume substantially its natural configuration, .Iadd.with said
tanning fluid being retained by said cusps of said heart valve,
.Iaddend.
applying such tanning fluid to the exterior of said unit .Iadd.so
that said tanning fluid engages substantially the entire exterior
surface of said heart valve .Iaddend.while said pressurized tanning
fluid is in said chamber with a greater fluid pressure existing in
said chamber than on said exterior,
and maintaining said pressurized tanning fluid and said tanning
fluid so applied to the exterior of said unit for a time sufficient
to cause the tissue of said valve to become substantially
fixed,
thereby to cause said valve to substantially maintain said
configuration.
. The heart valve as recited in claim 30 in which for introducing
said pressurized fluid into said chamber a source of said tanning
fluid is maintained at a predetermined height relative to said
unit, and in which a conduit is extended from said source of said
tanning fluid to said chamber to cause said tanning fluid at said
source to provide a predetermined
pressure head. 32. The heart valve as recited in claim 31 in which
said predetermined height is selected so as to provide a pressure
head of around 80 mm Hg. .[.33. Natural tissues for implantation
and in a form in which a portion thereof is subjected to pressure
within the physiologic range when implanted and which assumes a
predetermined configuration as a result of such pressure, said
tissues having full and uniform fixation and a relatively high
tensile strength, and prepared by the steps of
applying a tanning fluid to said portion of said tissues,
said tanning fluid so applied being under pressure in the
physiologic range so as to cause said tissues to assume
substantially said predetermined configuration,
and simultaneously applying a tanning fluid to remaining parts of
said tissues at a pressure less than that of said portion of said
tissues,
thereby to cause said tissues to assume said configuration during
fixation
of said tissues..]. .[.34. The tissues as recited in claim 33 in
which for so applying said tanning fluid to said portion of said
tissues with said tanning fluid being under pressure within the
physiologic range, a source of said tanning fluid under pressure is
provided, and a conduit is extended from said source to said
portion of said tissues, for thereby so applying said tanning fluid
to said portion of said tissues..]. .[.35. The tissues as recited
in claim 34 in which for said source of said tanning fluid under
pressure, a quantity of said tanning fluid is provided at a
predetermined height relative to said portion of said tissues..].
.[.36. A vessel for implantation having a contour different from
the contour thereof in its natural state prepared by the steps
of
subjecting said vessel to a bath of tanning fluid so as to fix said
vessel,
and simultaneously engaging said vessel with a guide member of
predetermined contour for causing said vessel to assume
substantially said predetermined contour upon fixation thereof,
said predetermined contour being different from the contour of said
vessel in its natural state..]. .[.37. Natural tissues for
implantation and in a form in which a portion thereof is subjected
to pressure within the physiologic range when implanted and which
assumes a predetermined configuration as a result of such pressure,
said tissues having full and uniform fixation and a relatively high
tensile strength, and prepared by the steps of
applying a tanning fluid to said portion of said tissues,
said tanning fluid so applied being under pressure within the
physiologic range so as to cause said tissues to assume
substantially said predetermined configuration,
and applying a tanning fluid to remaining parts of said tissues
while said tanning fluid under pressure is so applied to said
portion of said tissues,
so that said tissues experience a higher pressure at said portion
thereof than at said remaining parts thereof..]. .[.38. The tissues
as recited in claim 37 in which said preparation thereof includes
the step of engaging said tissues with a guide member of
predetermined contour while said tanning fluid under pressure
within the physiologic range is so applied to said portion of said
tissues for causing said tissues to assume substantially said
predetermined contour..]. .[.39. The tissues as recited in claim 38
in which said tissues constitute a vessel..]. .[.40. The vessel as
recited in claim 39 in which said vessel in its natural state has
substantially said predetermined contour..]. .[.41. The vessel as
recited in claim 39 in which said vessel in its natural state has a
contour different from said predetermined contour..]. .[.42. The
vessel as recited in claim 41 in which said predetermined contour
is substantially U-shaped..]. .[.43. The vessel as recited in claim
39 in which for said engaging of said vessel with a guide member,
an elongated element having substantially said predetermined
contour, and a lateral dimension less than that assumed by said
vessel when subjected to pressure within the physiologic range, is
inserted into said vessel for thereby maintaining said vessel
substantially in said predetermined contour..]. .[.44. The vessel
as recited in claim 39 in which for said engaging of said vessel
with a guide member, said vessel is placed within a tubular element
having substantially said predetermined contour and an interior
lateral dimension approximately that assumed by said vessel when
subjected to pressure within the physiologic range, for thereby
maintaining said vessel substantially in said predetermined
contour..]. .[.45. The vessel as recited in claim 39 in which for
applying said pressure to said vessel, the end and any collaterals
thereof are ligated, and said tanning fluid under pressure within
said physiologic range is introduced into the interior of said
vessel..]. .[.46. The vessel as recited in claim 39 in which for
introducing said tanning fluid under pressure within the
physiologic range into said vessel, a source of said tanning fluid
is maintained at a predetermined height relative to said vessel,
and a conduit is extended from said source of said tanning fluid to
said vessel to cause said tanning fluid at said source to provide a
predetermined pressure head..]. .Iadd. 47. The method as recited in
claim 2 in which, for so applying said tanning fluid to said
upstream end of said valve, said valve is submersed in a bath of
said tanning fluid. .Iaddend..Iadd. 48. The method as recited in
claim 7 in which, for so applying said tanning fluid to the
exterior of said unit, said unit is positioned in a bath of said
tanning fluid so that said tanning fluid of said bath engages
substantially the entire outer surface of said valve. .Iaddend.
.Iadd. 49. The method as recited in claim 7 in which,
for so applying said tanning fluid to the exterior of said unit,
said unit is positioned in a tank containing said tanning fluid so
that said tanning fluid of said tank engages substantially the
entire outer surface of said heart valve,
and in which for so introducing said pressurized tanning fluid into
said chamber
a reservoir containing said tanning fluid is maintained at a
predetermined height above said unit,
and a conduit is extended from said reservoir to said aperture of
said member to cause said tanning fluid of said reservoir to
provide a predetermined pressure head within said chamber.
.Iaddend. .Iadd. 50. The method of simultaneously preparing a
plurality of natural heart valves for implantation so that said
valves will have improved tensile strength, will have and retain
generally regular contours with their cusps closed as in diastole,
and will be substantially in their natural configurations, so that
said valves will remain competent for prolonged periods of use upon
implantation comprising the steps of
excising from a plurality of donor hearts a plurality of units each
of which includes a heart valve and its ascending aorta, then
inserting into each of said ascending aortas a member having an
aperture therethrough, attaching said aorta of each of said units
to the one of said members inserted therein so that said units and
said members define chambers,
ligating the arteries of each of said units so as to close said
chambers,
attaching said members to a manifold,
connecting a source of pressurized tanning fluid to said manifold
so that said pressurized tanning fluid is introduced simultaneously
into said chambers through said apertures of said members and
exerts in said chambers a pressure which is within the physiologic
range of pressure for said valves,
thereby to inflate said valves and cause them to assume generally
regular contours with their cusps coapted and closed as in diastole
so that said valves are in substantially their natural
configuration with said tanning fluid being retained in said
chambers by the cusps of said heart valves,
positioning said manifold adjacent a tank containing a quantity of
said tanning fluid so that said valves are submerged in said
tanning fluid in said tank and said tanning fluid engages
substantially the entire outer surfaces of said heart valves, while
said source of pressurized tanning fluid is so attached to said
manifold and exerts a greater fluid pressure in said chambers than
on said outer surfaces of said valves,
and maintaining said source of pressurized tanning fluid so
connected to said manifold and said manifold so positioned adjacent
said tank for a time sufficient to cause the tissues of said valves
to become substantially fixed,
thereby to cause said valves to substantially maintain said
configurations
and to have improved tensile strength. .Iaddend. .Iadd. 51. The
method as claimed in claim 50 including the steps of inspecting
said valves while said source of pressurized tanning fluid is so
connected to said manifold to detect loss of said pressurized
tanning fluid through said valves, and discarding those of said
valves through which there is an excessive loss of said pressurized
tanning fluid. .Iaddend. .Iadd. 52. In the method of replacing a
diseased heart valve in a human patient with a natural tissue valve
taken from an animal or a human wherein the natural tissue valve is
fixed prior to implantation by exposure to a tanning fluid and
thereafter mounted on a stent or affixed directly to the annulus of
the heart of the patient, the improvement comprising
applying a tanning fluid under pressure in the physiologic range to
the downstream end of said natural tissue valve so as to cause said
valve to assume substantially its natural configuration,
and simultaneously applying a tanning fluid to the upstream end of
said valve and to substantially the entire exterior surface of said
valve at a pressure less than that at said downstream end,
thereby to cause said valve substantially to maintain said
configuration during fixation of the tissue thereof.
.Iaddend..Iadd. 53. In the method of replacing a diseased heart
valve in a human patient with a natural tissue valve taken from an
animal or a human wherein the natural tissue valve is fixed prior
to implantation by exposure to a tanning fluid and thereafter
mounted on a stent or affixed directly to the annulus of the heart
of the patient, the improvement comprising
applying a tanning fluid under pressure within the physiologic
range to the downstream end of said natural tissue valve so as to
cause said valve to assume substantially its natural
configuration,
applying said tanning fluid to the upstream end of said valve while
said tanning fluid under pressure is so applied to said valve at
the downstream end thereof so that said valve is at a higher
pressure from said tanning fluid at said downstream end than at
said upstream end,
and maintaining said tanning fluid so applied to said valve for a
time sufficient to cause said valve to become fixed so as to
substantially maintain said configuration. .Iaddend..Iadd. 54. The
method as recited in claim 53 in which said pressure is
substantially within the range of from about 80 to about 120 mm Hg.
.Iaddend. .Iadd. 55. The method as recited in claim 53 in which
said tanning fluid under pressure is applied to said valve by
maintaining a quantity of said tanning fluid so as to have a
predetermined maximum height with respect to said valve, and
connecting said quantity of tanning fluid to said valve so that
said quantity of tanning fluid produces a pressure head applied to
said valve. .Iaddend..Iadd. 56. The method as recited in claims 1,
2, 7, 53 or 54 in which said tanning fluid is a glutaraldehyde
solution. .Iaddend..Iadd. 57. In the method of replacing a diseased
heart valve in a human patient with a natural tissue valve taken
from an animal or a human wherein the natural tissue valve is fixed
prior to implantation by exposure to a tanning fluid and thereafter
mounted on a stent or affixed directly to the annulus of the heart
of the patient, the improvement comprising
excising from a donor heart a unit that includes a heart valve and
its ascending aorta,
then inserting into said ascending aorta above said heart valve a
member having an aperture therethrough,
attaching said aorta to said member so that said unit and said
member define a chamber closed at one end by the cusps of said
heart valve and said apertures provides access to the interior of
said chamber at the downstream end of said valve, ligating the
arteries of said unit so as to close said chamber, introducing a
glutaraldehyde solution which is pressurized to substantially
within the range of 80 mm Hg to 120 mm Hg pressure through said
aperture into said chamber so as to inflate said valve and cause
said valve to assume substantially its natural configuration, with
said glutaraldehyde solution being retained by said cusps of said
heart valve,
applying a glutaraldehyde solution to the exterior of said unit so
that said glutaraldehyde solution engages substantially the entire
exterior surface of said heart valve while said pressurized
glutaraldehyde solution is in said chamber, with a greater fluid
pressure existing in said chamber than on said exterior,
and maintaining said pressurized glutaraldehyde solution in said
chamber and said glutaraldehyde solution so applied to the exterior
of said unit for a time sufficient to cause the tissue of said
valve to become substantially fixed,
thereby to cause said valve to substantially maintain said
configuration. .Iaddend..Iadd. 58. The method as recited in claim
57 in which for introducing said glutaraldehyde solution into said
chamber a source of said glutaraldehyde solution is maintained at a
predetermined height relative to said unit, and in which a conduit
is extended from said source of said glutaraldehyde solution to
said chamber to cause said glutaraldehyde solution at said source
to provide a predetermined pressure head. .Iaddend..Iadd. 59. The
method as recited in claim 58 in which said predetermined height is
selected so as to provide a pressure head of around 80 mm Hg.
.Iaddend.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the preparation of natural tissue for
implantation.
2. Description of Prior Art
Natural aortic valves taken from animals or humans have been used
for a number of years for allo and xenograft replacement of
diseased valves. This has experienced only limited success,
however, as in a large proportion of cases the replacement valves
develop leakage. The incidence of incompetency has run from 40% to
80%. This occurs primarily because the valve is a very flexible and
elastic structure which does not maintain its normal physiologic
state when removed from the donor heart. This readily distortable
element must then be matched with the flexible structure of the
patient's heart, which also is not in its normal physiologic state
when prepared for the valve replacement. With distortion of the
flexible valve being unavoidable, and with no two valves being the
same, it becomes virtually impossible to affix the valve to a stent
or the patient's annulus at the proper location to maintain the
valve's natural configuration. Consequently, undesirable stresses
are introduced into the valve. This may result in immediate
incompetence of the valve. Even where this does not prevent
competence initially, the existence of the stresses in the valve
over a period of time frequently causes premature failure.
If an appropriate tanning fluid is applied to a natural heart
valve, its tissue becomes fixed so that it loses its characteristic
of extreme flexibility and elasticity. As a result, in order to
assure retention of approximately normal geometry, the cusps of the
allo and xenograft valves have been packed with cotton, and the
valves then have been fixed by tanning. This, however, has not
solved the problem of valve failure because it never has been
possible to impart exactly its natural configuration to a valve by
packing it with cotton or similar material. Consequently, there are
inevitably variations from the normal valve shape, and these
differences become fixed in the valve by the tanning operation.
These shape variations introduce stresses in the valve, which may
cause it to fail subsequently.
Another problem encountered from such tanning of the valve is that
shrinkage occurs as a result of this procedure. The amount of
shrinkage is not the same in different valves, so that there is no
way of predicting how much shrinkage will take place. Later, when
the valve is exposed to biologic fluid after it has been implanted,
it experiences some re-expansion. Again, this is an unknown amount.
These factors contribute to the difficulty in properly mounting the
valve and make the introduction of undesirable stresses practically
unavoidable.
Similar problems have been encountered with vessels which also have
been prepared for implantation by fixation with a tanning fluid.
Problems have included inadequate penetration of the fixative, a
lack of uniformity of fixation and insufficient tensile strength in
the prepared vessels.
SUMMARY OF THE INVENTION
The present invention overcomes the difficulties previously
encountered with natural valves, vessels and the like. It permits a
natural heart valve to be fixed in its natural state so that it
will retain its shape and can be readily and correctly mounted on a
stent or affixed directly to the annulus of the heart of the
patient. By this procedure, the valve is subjected to fluid
pressure and at the same time fixed by exposure to a tanning fluid.
It has been found that, when fluid pressure is applied to a valve
after removal from the heart, the valve will be given its natural
shape. Therefore, when fixed in a pressurized condition, the valve
will retain its normal architecture, allowing proper mounting to be
achieved. Similarly, vessels are subjects to pressure while being
fixed with comparable improved results.
The valve may be pressurized by introducing the tanning fluid into
it while subjecting the exterior of the valve to a bath of the same
tanning fluid. In accomplishing this, the valve and associated
ascending aorta are excised from the donor heart and attached to a
stopper which has an opening through it. The tanning fluid is
introduced through this opening into the interior of the valve, and
a normal physiologic pressure is applied. This may be accomplished
accurately by providing a source of the tanning fluid at a
predetermined height with respect to the valve, so that the
pressure head on the valve is at the correct value. After an
appropriate period in the tanning solution, the valve is fixed in
its natural contour and, upon removal, will retain this shape.
Then, upon trimming, it is ready for mounting on a stent or for
attachment to the heart of the patient. The prepared valve also may
be stored frozen for future use or stored in the solution.
When fixed under pressure in this manner, the valve does not shrink
during the tanning process, nor does undesirable expansion occur
subsequently when the valve is subjected to the biologic fluid. The
tanning process takes place more rapidly when the tanning solution
is under pressure. Also, when tanned under pressure, the tensile
strength of the tissue of the valve becomes increased. Improved
results are obtained additionally because, when subjected to the
pressure of the tanning fluid, valves that inherently will leak may
be detected through the loss of fluid through the valve. These may
be discarded to that only properly functioning valves will be
retained for subsequent implantation.
In preparing a vessel, the collaterals and one end are ligated, and
the other end is attached to a source of pressurized tanning fluid.
While the interior of the vessel is subjected to the pressurized
tanning fluid, the exterior is submersed in a bath of the tanning
fluid. The natural overall contour of the vessel may be maintained
as it is fixed by engaging it with a guide having the same general
shape as the natural vessel contour. The guide also may impart a
different contour to the vessel so that special shapes can be
produced. The guide may be a rod received within the vessel or a
tube surrounding the vessel.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a longitudinal sectional view of a valve structure
attached to a device for applying pressurized tanning fluid and
after being fixed by the tanning fluid;
FIG. 2 is an elevational view, partially in section, illustrating
an arrangement for treating a number of valves;
FIG. 3 is a top plan view showing the manifolding arrangement for
distributing the tanning fluid;
FIG. 4 is a sectional view taken along line 4--4 of FIG. 1;
FIG. 5 is a view similar to FIG. 4 but illustrating the appearance
of a valve in the absence of treatment in accordance with this
invention;
FIG. 6 is a side elevational view, partially in section,
illustrating the arrangement for fixing vessels for implantation,
utilizing straight rods for maintaining the configurations of the
vessels;
FIG. 7 is an enlarged fragmentary view of a portion of the
arrangement of FIG. 6, the vessel being shown internally
pressurized;
FIG. 8 is a view similar to FIG. 7 but of a vessel receiving a
curved rod as a guide member, with the vessel shown pressurized;
and
FIG. 9 is a view similar to FIGS. 7 and 8, but with a tube used to
guide the vessel, and with the vessel shown unpressurized.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In preparation for a transplant, an aortic valve 10 is excised
along with the ascending aorta 11 and extraneous tissue removed.
This includes removal of the aorta above the sinus of the Valsalva,
the annulus and subvalvular structure. The coronary arteries 12 are
ligated by sutures 13. The aorta 11 then is extended around a
rubber stopper 15, which has a central axially extending opening 16
through it. The stopper 15, therefore, is positioned in the aorta
11 above the valve 10, between the valve and the arch of the aorta.
A suture 17 is wrapped around the exterior to affix the aorta to
the stopper 15. The result is the formation of a chamber 19 within
the valve structure, closed at its lower end by the cusps 20 of the
valve. Access to the upper portion of the chamber 19 is provided by
the opening 16 through the stopper 15. This allows pressurized
tanning fluid to be introduced into the chamber 19 to fix the valve
10 in its natural configuration.
In order to pressurize the valve, the arrangement shown in FIGS. 2
and 3 may be employed, which provides a means for treating a number
of valves simultaneously. This system includes an open-topped tank
22 from the bottom of which extends a line 23 to a pump 24. The
latter, through a conduit 25, connects to a reservoir 26 that is
located above the tank 22. A filter 27 in the line 25 will remove
any impurities in fluid conducted through the line 25 to the
reservoir 26. Extending downwardly from the reservoir 26 is a line
28, the lower end of which connects to a main manifold 29. A
shutoff valve 30 may be included in the line 28. Additional and
smaller manifolds 31 extend outwardly from the main manifold 29,
each of these being provided with a plurality of downwardly
extending stems 32. The openings 16 of stoppers 15 to which valve
elements have been attached receive the open lower ends of the
stems 32. This positions the valve structures 10 within the tank
22.
A suitable tanning fluid 33, such as formaldehyde, glutaraldehyde
or other aldehyde, is introduced into the tank 22 and the reservoir
26. The fluid 33 in the tank 22 covers the exteriors of the valve
structures 10. This causes the upstream ends of the valves 10 to be
submerged in the tanning fluid 33.
The fluid 33 from the reservoir 26 fills the interior chambers 19
of the valves 10, where it is retained by the cusps 20. Because the
reservoir 26 is elevated with respect to the location of the valves
10, a static pressure head is developed which causes the tanning
fluid in the chambers 19 to exert pressure against each of the
valves 10. This fluid pressure applied from the proximal aorta,
being thus on the downstream side of the valve 10, inflates the
valve and causes the valve to assume its natural contour. The
maximum elevation of the fluid 33 in the reservoir 26 is kept at a
height to produce a pressure head such that the valves will be
pressurized within the physiologic range. This is from 80 to 120 mm
Hg, with 80 mm Hg being used most frequently as the pressurizing
value. The pressurization is controlled accurately and changed as
needed by selecting an appropriate elevation of the reservoir 26
over the tank 22 to result in a desired pressure head. This
pressure is maintained within the chambers 19 of the valve
structures for a period sufficient to attain a fixation of the
tissue of the valves. In a 4% formaldehyde solution or a 0.2%
glutaraldehyde solution, this will occur in around 72 hours.
After being maintained under fluid pressure in the presence of the
tanning fluid, the valve is removed and then may be handled without
disturbing its natural geometry. It is then ready for mounting on a
stent or for being affixed in the annulus of the heart of a
patient. The natural shape of the valve may be maintained without
difficulty as it is mounted, because any distortion is visually
apparent. The valve will keep its shape when prepared in this
manner, exhibiting neither shrinkage from the preparation nor
expansion from subsequent contact with biologic fluid. The chance
of incompetence, even after a prolonged period of subsequent use,
is greatly reduced. The tissue of the valve achieves a higher
tensile strength as a result of the tanning under pressure for
greater life and assured performance. Furthermore, the process
serves for quality control as valves exhibiting excess leakage can
be detected and discarded. In the event that leakage past the cusps
20 of the valves 10 raises the level of the fluid 33 in the tank 22
too high, the excess is returned to the reservoir 26 by the pump
24.
In appearance, the prepared valve will resemble the illustration of
FIG. 4 with a generally regular contour and coaptation of the cusps
20. The cusps are closed as in diastole, and the valve is in its
normal physiologic state. Without the treatment in accordance with
this invention, the valve may appear generally as shown in FIG. 5,
with an uneven contour and the potential of leakage through the
cusps.
The process of this invention as used in preparing arteries and
veins for implantation may be seen in FIGS. 6 and 7. Here, one end
of a vessel 35 is fitted over the downwardly extending stem 36 of a
fluid manifold 37, held to it by means of sutures 38. The manifold
37 may be generally similar to the manifold 31 described above. The
vessel 35 is received within a shallow tank 39 containing the
tanning fluid 33. The other end 40 of the vessel 35 is ligated by
sutures 41, and its collaterals 42 are ligated by sutures 43. This
causes the vessel 35 to define an enclosed chamber. Within the
interior of the vessel 35 is a straight rod 44, which extends the
major part of the length of the vessel. The rod 44 is made of a
suitable inert material, such as glass or a plastic such as
polyolefin, and is of a constant outside diameter. The diameter of
the rod 44 is less than that the vessel 35 assumes when it is under
its normal physiologic pressure. The rod, however, serves to keep
the vessel 35 straight under all conditions, this being the natural
configuration for the vessel illustrated.
The manifold 37 is connected through a line 45 to an elevated
reservoir of tanning fluid or other source of tanning fluid under
pressure within the physiologic range. The internally applied
tanning fluid inflates the vessel 35 so that during its period of
fixation it assumes generally the normal diameter of a pressurized
vessel. The tanning fluid in the tank 39 is applied to the exterior
of the vessel 30 simultaneously to the internal pressurization with
tanning fluid from the manifold 37. When treated in this manner,
the vessel 35 has an improved shape, greater tensile strength and
more uniformity of fixation with a greater penetration of the
fixative than if conventional fixing procedures are followed.
The rod within the vessel need not be straight, but may be shaped
to other contours to correspond to a desired overall configuration
for the vessel. As shown in FIG. 8, the rod 46 is U-shaped,
maintaining that contour for a vessel 47 which in its natural state
has a different shape. Again, the end 48 of the vessel 47 is
ligated as are its collaterals 49. The vessel is immersed in the
tanning fluid 33 and attached to the manifold stem 36, as before.
Pressure then is applied to the interior of the vessel during its
period of fixation. When the tanning operation is complete, the
vessel will retain substantially the U-shaped contour of the rod
46. This enables specially shaped natural vessels to be produced to
suit particular requirements. The U-shaped vessel, for example, can
be used as a shunt between vein and artery during kidney
dialysis.
Instead of a rod within the vessel, a tube may be placed around the
vessel to perform a similar function of maintaining it in a desired
configuration. In FIG. 9 there is shown a U-shaped tube 50 of
constant diameter surrounding a vessel 51, which has a natural
shape differing from that of the tube. The tube 50 has a greater
diameter than that of the vessel 51 before its interior is
pressurized, as shown. However, pressurization of the vessel 51
will expand it to approach the lateral dimension of the tube 50.
The tube 50 keeps the vessel 51 in the proper shape throughout the
tanning process.
Other configurations of rod or tube may be devised to accommodate
vessels to be fixed either in their natural shapes or in different
shapes. Bifurcations, trifurcations and the like are possible
utilizing a tube as the guiding element.
The foregoing detailed description is to be clearly understood as
given by way of illustration and example only, the spirit and scope
of this invention being limited solely by the appended claims.
* * * * *