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.

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.