Abstract:
A replacement heart valve and fixture assembly for limiting longitudinal stretch during fixation of a harvested aortic root including valve leaflets. The assembly includes an inflow plug inserted into the inflow section of the aortic root and having an apertured tube or cannula extending through the valve leaflets to an outflow plug inserted into the outflow section of the aortic root. Apertures in the tube are located on either side of the valve leaflets and the tube is coupled to a fluid inlet, preferably located on the outflow plug. The outflow plug is slidable relative to the tube and is provided with an engagement mechanism such as a setscrew for fixing the location of the outflow plug relative to the tube and the inflow plug.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application is a continuation of Ser. No. 10/131,979, HEART VALVE FIXATION PROCESS AND APPARATUS, filed Apr. 25, 2002. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    The present invention relates to the production of tissue heart valves generally and more particularly to fixtures for use in conjunction with fixation of valve tissue.  
           [0003]    Tissue heart valves may be fabricated by harvesting a mammalian aortic root including the aortic valve and thereafter fixing the harvested aortic root to crosslink the tissue. Thereafter, the aortic root may be trimmed and employed as heart valve for implantation in human beings. The valve may be mounted to a stent or frame, for example as disclosed in U.S. Pat. No. 5,824,069, issued to Lemole, U.S. Pat. No. 4,816,029, issued to Penney, et al., U.S. Pat. No. 5,716,401, issued to Eberhardt, et al. or U.S. Pat. No. RE 30,912, issued to Hancock. Alternatively, the valve may be implanted without an associated stent, as described in U.S. Pat. No. 5,336,258, issued to Quintero, et al or U.S. Pat. No. 6,074,419, issued to Healy, et al.  
           [0004]    U.S. Pat. No. 5,824,060 issued to Christie, et al. and incorporated herein by reference in its entirety describes a process for heart valve fixation, in which the harvested aortic root is subjected to a fixative fluid to provide a first differential fluid pressure across the tubular wall of the outflow section of the aortic root and a second differential fluid pressure across the valve leaflets. As disclosed, the inflow and outflow sections of the aortic root are coupled to fluid couplings that are in turn coupled to sources of fixative fluid under pressure. The entire assembly is also placed in fixative fluid during the fixation process.  
           [0005]    U.S. Pat. No. 5,830,239 issued to Toomes and incorporated herein by reference in its entirety describes an improvement to the process of the &#39;060 patent, in which only the outflow section of the aortic root is mounted to a fluid coupling and the inflow section of the root is blocked by a plug. The plug is provided with a tube or cannula having an inlet portion extending through the valve leaflets and an outlet opening located in the inflow section of the aortic root, allowing fixative fluid to flow through the valve so that fluid may be applied to both sides of the valve and to the inflow and outflow sections of the aortic root. The fluid coupling is coupled to a source of fixative and the entire assembly is placed in fixative during the fixation process. The process disclosed in the &#39;239 patent substantially simplifies the fixturing process as compared to the &#39;060 patent.  
         SUMMARY OF THE INVENTION  
         [0006]    The present invention is an improvement to the process described in the &#39;239 patent, providing a way to control axial stretch of the aortic root during the fixation process. Because the stretch of the aortic root is controlled, the fixturing system and process of the present invention is intended to produce an increased yield as compared to the process in the &#39;239 patent.  
           [0007]    The fixturing system of the present invention resembles that as described in the &#39;239 patent, in that only a single fluid coupling is employed, preferably part of an outflow plug coupled to the outflow section of the aortic root, and in that the inflow section of the aortic root is blocked by an inflow plug. However, in the present invention, the cannula or tube extending from the inflow plug extends through the valve all the way to the outflow plug. The tube smoothly slides into the outflow plug, allowing for adjustment of the relative positions of the inflow and outflow plug. The outflow plug preferably has a setscrew or other mechanism associated therewith for fixing the location of the inflow plug relative to the ouflow plug. The tube is provided with a series of holes extending along of the tube and arranged to be located on both sides of the valve leaflets, so that a zero pressure differential across the leaflets can be achieved during fixation.  
           [0008]    In use, the outflow section of the aortic root is preferably first coupled to the fluid coupling, which in the preferred embodiment of the invention is part of an outflow plug, around which the outflow section of the aortic root is mounted. The fluid coupling is then coupled to a source of compressed air to close the valve leaflets and a contour ring is placed around the inflow section of the aortic root. The aortic tissue at the end of the inflow section of the aortic root is then folded back over the contour ring and a length of plastic tubing is slid over the tissue and contour ring and is maintained in place, for example, by means of a cable tie. Other mechanisms for restraining the outflow section of the aortic root during fixation may be substituted for the contour ring or the contour ring might, in some embodiments, be attached without prior application of pressure to close the valve leaflets.  
           [0009]    The apertured tube or cannula and the attached inflow plug are then inserted into the aortic root with the tube passing through the valve leaflets and engaging the fluid coupling. The inflow plug attached to the tube is located within the plastic tubing and attached to it by means of cable ties or the like, compressing the tubing around the inflow plug. The fluid coupling is then again attached to a source of compressed air, which is used to inflate the aortic root to a desired pressure and the setscrew is employed to fix the outflow plug to the tube, correspondingly stabilizing the relative location of the inflow and outflow sections of the aortic root and preventing excessive longitudinal stressing during fixation. The assembly is then moved to a fixative bath where the outflow plug is coupled to a source of fixative under pressure, and the assembly is placed into the fixative bath during the fixation process. On completion of fixation, the aortic root is removed and trimmed and may thereafter be mounted to an associated heart valve stent. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    [0010]FIG. 1 shows a cross section of a harvested porcine aortic root mounted to the outflow plug of the present invention.  
         [0011]    [0011]FIG. 2 shows the aortic root and outflow plug of FIG. 1 inverted so that the outflow plug may be coupled to a source of compressed air to close the valve leaflets and allow placement of the contour ring.  
         [0012]    [0012]FIG. 3 shows the assembly of FIG. 2 after addition of a length of plastic tubing, mounted around the contour ring and inflow section of the aortic root.  
         [0013]    [0013]FIG. 4 shows the assembly of FIG. 3 to which the inflow plug and associated tube have been mounted.  
         [0014]    [0014]FIG. 5 illustrates the assembly of FIG. 4 mounted in a fixative bath. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0015]    [0015]FIG. 1 is a cut away view illustrating a harvested porcine aortic root  10  mounted to outflow plug  20 . The aortic root includes the leaflets  12  of the aortic valve, an outflow section  14  and an inflow section  16 . In the fixation method of the present invention, the outflow section  14  is first mounted to the outflow plug  20  by inserting the plug  20  into the outflow section  14  and compressing the outflow section around the plug  20  by means of a cable tie  22  or the like.  
         [0016]    The outflow plug  20  is provided with a fluid coupling  24 , including a fluid inlet lumen  26 . Also included in outflow plug  20  are a threaded setscrew  28  and an o-ring  30 . As discussed above, the setscrew functions to lock the position of the outflow plug  20  relative to the tube or cannula and the attached inflow plug (not illustrated). As such, the screw  28  is sized so that when its end is engaged with the tube extending through the input passage  26 , O-ring  30  will be compressed to provide a fluid seal to prevent leakage of fixative or air, along the threads of the screw  28 .  
         [0017]    [0017]FIG. 2 is a cut away view of the assembly of FIG. 1, inverted to allow attachment to a source of compressed air via fluid coupling  24 . Other numbered items correspond to identically numbered items in FIG. 1. The process according to the present invention continues from the previous steps illustrated in FIG. 1 as follows. Fluid coupling  24  is coupled to a source of compressed air at approximately two inches H 2 O of pressure. This serves to close the leaflets  12  of the aortic valve, maintaining the aortic root in a position in which the leaflets properly coapt. Contour ring  32  is then slid over the inflow section  16  of the aortic root  10 , and the end of the inflow section is folded over the contour ring  32 . As described in the above cited &#39;239 et al patent, contour ring  32  serves to maintain the configuration of the aortic root in the vicinity of the leaflet bases in an appropriate configuration to assure valve coaption after fixation.  
         [0018]    [0018]FIG. 3 illustrates the apparatus in FIG. 2, during the next steps of the process according to the present invention. All numbered items correspond to identically numbered items if FIG. 2. After placement of the contour ring  32  around the inflow section  16  of the aortic root  10 , a plastic tube  36  which can be fabricated, for example, of silicone rubber is slid over the inflow section  16  and the contour ring  32  and is maintained in place by means of a cable tie  34  or the like as illustrated. Silicone tube  36  will serve to mount the inflow plug and associated tube, as discussed below.  
         [0019]    [0019]FIG. 4 illustrates the next step in the process according to the invention, and includes the apparatus illustrated in FIG. 3 above. Numbered components correspond to identically numbered components in FIG. 3 above.  
         [0020]    Inflow plug  38  and associated tube  42  have been added to the assembly of FIG. 3 above. The inflow plug  38  is sealed within plastic tube  36  by means of one or more cable ties  40  or the like. The plug thus effectively seals the inflow section of the aortic root  10  against leakage. Apertured tube  42 , mounted to inflow plug  38 , extends through the aortic valve leaflets  12 , and outward through the fluid inlet lumen  26  in fluid coupling  24 . Fluid inlet  24  is then coupled to a source of compressed air, preferably at about 10 plus or minus 1 inches H 2 O. The pressurized air is delivered to the interior of the aortic root in both the outflow and inflow sections, primarily by means of holes  44  in tube  42 . The air pressure serves to inflate the aortic root to a desired, but limited degree. During inflation, tube  42  is free to slide within the internal lumen  26  of fluid inlet  24  to an optimal position for fix ation. The inlet and outflow plugs  38 ,  20  and the attached aortic root  10  are now in the desired configuration for the fixation process.  
         [0021]    After inflation of the aortic root, setscrew  28  is tightened against tube  42  to lock it in position relative to the outflow plug  20  and fluid coupling  24 . 0-ring  30  is concurrently compressed to seal against fluid losses during fixation that might otherwise occur around the threads of screw  28 . The assembly is now ready to be placed in the fixative bath and attached to a source of fixative. It has been determined that allowing inflation of the valve to determine the spacing of the inflow and outflow plugs provides for a procedure which produces preserved porcine aortic roots without undue longitudinal stretching, improving the yield of the process.  
         [0022]    [0022]FIG. 5 is a cut away view illustrating the fixation portion of the process according to the present invention. In this view, the assembly illustrated in FIG. 4 is inverted and placed in a fixative bath  50 , containing fixative  52  which may be, for example, a 0.2% aqueous solution of gluteraldehyde. Other fluid fixatives (liquid or gaseous), as disclosed in U.S. Pat. No. 5,880,242, issued to Hu, et al., U.S. Pat. No. 5,733,339, issued to Girardot, et al., U.S. Pat. No. 5,376,110, issued to Tu, et al., U.S. Pat. No. 5,447,536, issued to Girardot, et al., U.S. Pat. No. 5,931,868, issued to Gross, et al. or U.S. Pat. No. 4,880,603, issued to Jaffe, all incorporated herein by reference in their entireties, may also be employed in conjunction with the method of the present invention. The fluid inlet  24  is coupled to a source of fixative under pressure, for example, the same as fixative  52 , but under pressure. The fixative is delivered to the interior of the aortic root via the holes  44  in tube  42 . The assembly remains in the fixative bath with pressurized fixative applied via the fluid coupling  24  until fixation is complete. Fixation times will vary as a function of the pressures and fixatives employed. Anti-calcification treatments, for example using alpha-aminooleic acid as described in U.S. Pat. No. 4,976,733, issued to Girardot, et al. and incorporated herein by reference in its entirety, may also be employed.  
         [0023]    In a preferred embodiment of the invention using a porcine aortic root, the pressure the fixative solution provided via the fluid coupling  24  is adjusted to provide a pressure drop across the walls of the aortic root of about 40 mm Hg. However, as described in the &#39;060 and &#39;239 patents cited above, the pressure drop may be substantially higher or lower, e.g. 20-120 mm Hg. The desired pressure drop may also vary as a function of the species from which the aortic root was harvested. Because the fluid is delivered at equal pressure to both sides of the aortic valve leaflets  24 , there is effectively a zero pressure drop across the valve leaflets. The pressure drop across the walls of the aortic root is determined by the difference between the inlet pressure at fluid inlet  24  and the pressure of the fixative solution  52  in the fixative bath  50 . While FIG. 5 illustrates a single fixture and aortic root assembly located in a fixation tank, it should be understood that in commercial embodiments of the present invention, multiple such assemblies will be coupled to piccolo tubes as described in the above-cited &#39;239 patent, and simultaneously fixed within a larger fixative bath.  
         [0024]    It should be noted that while the disclosed embodiment employs a setscrew to fix the tube to the fluid coupling, other mechanisms such as clamps, collets, pins, cams, detents or other devices may be substituted. Further, while in the embodiment as described, the pressure differential across the walls of the aortic root is kept generally constant during the fixation process, pulsatile or varying pressure may in some cases be employed. In addition, while in the preferred embodiment, the fluid coupling is mounted to the inflow plug and extends through the outflow plug, it is possible that a reversal of these elements so that the fluid coupling is associated with the. Finally, while inflation of the aortic root to establish the desired spacing of the inflow and outflow plugs, it is believed that the invention might still be usefully practiced in embodiments in which some other method, e.g. mechanically stretching the root to a desired length or tension, is used to determine the desired spacing. As such, the above-disclosed embodiment should be considered as exemplary, rather than limiting in conjunction with the claims that follow.