A juvenile sheep model for the long-term evaluation of stentless bioprostheses implanted as aortic root replacements.

BACKGROUND AND AIM OF THE STUDY: Orthotopic valve replacement in large animals is an important component of the preclinical assessment of bioprosthetic valves. To provide the most useful preclinical information, the development of models that parallel clinical practice patterns is essential. Therefore, we sought to develop a technically feasible and reproducible model for chronic evaluation of stentless bioprosthetic aortic valves implanted as aortic root replacements in juvenile sheep. METHODS: Juvenile domestic sheep (mean age 21+/-2.28 weeks; range: 17-26 weeks) underwent aortic root replacement using standard cardiopulmonary bypass (CPB) and surgical techniques. Animals were implanted with 19 mm (n = 21), 21 mm (n = 18) or 23 mm (n = 4) bioprostheses from two different manufacturers, and followed for 150 days. Animals surviving at least 150 days were considered long-term survivors; those which died prior to postoperative day (POD) 31 were considered operative deaths. RESULTS: Forty-three animals underwent aortic root replacement. The mean CPB time was 91+/-20 min (range: 62-149 min); mean cross-clamp time was 63+/-13 min (range: 39-95 min). Thirty-five animals (81%) survived the first 30 days of the study period. Five deaths occurred at POD 0 due to anastomotic complications. One death occurred each on POD 3, 6, and 26 as a result of prosthesis size mismatching, thromboembolic complications, and endocarditis, respectively. There were five late deaths. Twenty animals survived the minimum 150-day study period, and 12 were sacrificed at 183+/-17 days. Six animals remain alive at 151+/-0.98 days, and one animal died each on POD 184 and 190. The remaining 10 animals are not yet 150 days from their operation. Currently, all are well at 102+/-34 days (range: 33-140) days. CONCLUSION: These data suggest that long-term evaluation of stentless aortic bioprostheses implanted as aortic root replacements can be accomplished using juvenile sheep.

A novel annuloplasty system with rigid and flexible elements: initial experimental results in sheep and the case for untreated autologous pericardium.

BACKGROUND AND AIMS OF THE STUDY: A precise annuloplasty is difficult to perform with pericardium as the ring material because unwanted plication of the pericardium itself typically occurs when the sutures are tied. A novel annuloplasty system has been developed which should allow a predictably precise measured plication of the annulus without plication of the pericardium itself. A feasibility study was designed to evaluate this new concept. METHODS: Three juvenile sheep underwent implantation of a new annuloplasty system into the posterior mitral annulus without tissue annulus plication. Small rigid titanium suture-platforms 7 x 3 x 1 mm with two-suture holes 3 mm apart were individually affixed to the posterior mitral tissue annulus each with a single horizontal mattress suture. A longitudinal strip of untreated autologous pericardium, corresponding to the perimeter dimension of the free edge of the anterior leaflet, was sutured to the posterior annulus including both fibrous trigones, covering the suture-platforms with the mesothelial surface up, using two different suture techniques. No postoperative anticoagulation was utilized. Serial transthoracic echocardiograms and necropsy at five to six weeks post implant were performed. RESULTS: When the pericardium was affixed to the annulus with a continuous suture exposing only the mesothelial surface to the blood, completely covering the suture-platforms and their suture knots or folded in upon itself as a tube above the suture-platforms, it appeared to maintain all of its original implant dimensions and flexibility. There was no functional or anatomical distortion of any part of the mitral apparatus; fibrotic reaction was minimal and there was no thrombus formation with this suture technique. CONCLUSIONS: This annuloplasty system, combining rigid and flexible elements, 'melts' into the tissue annulus with a low profile, providing overall annular flexibility with no shrinkage of the overlying untreated autologous pericardium, no distortion of any part of the mitral apparatus, minimal fibrous reaction and no thrombus formation.

Feasibility evaluation of a new pericardial bioprosthesis with dye mediated photo-oxidized bovine pericardial tissue.

BACKGROUND AND AIMS OF THE STUDY: In an attempt to overcome the problem of calcification of bioprostheses, a novel bovine pericardial tissue valve preserved with a non-aldehyde, dye mediated photo-oxidation process (PhotoFixTM) developed by CarboMedics, Inc. The device was evaluated by implantation in the mitral position of juvenile sheep with a mean age of 3.5 months. MATERIALS AND METHODS: Thirteen valves were evaluated; six experimental valves with photo-oxidized tissue, five identically designed valves with glutaraldehyde-fixed tissue, and two Carpentier-Edwards pericardial valves as controls. RESULTS: Four of the six animals in the photo-oxidized group were free of calcification when electively sacrificed at 152 days, 152 days, one year and 1.5 years respectively. One animal was electively sacrificed at 98 days. Pathologic findings indicated minimal calcification of the valve due to uneven stress distribution from two bent stent posts that most likely occurred during surgical implantation, but the device was still functional. The sixth animal with photo-oxidized tissue died at 131 days due to massive calcification of a single leaflet. There was no pathologic evidence of infection. Explants at five months from additional and still continuing sheep studies per FDA guidelines have not reproduced single leaflet calcification in over forty explanted valves with photo-oxidized tissue. The glutaraldehyde-fixed valves all exhibited some calcification at explant; two of these animals died early due to the mineralization. Both control animals with Carpentier-Edwards valves died early from mitral stenosis due to extensive device calcification. CONCLUSIONS: The fact that four of six valves with photo-oxidized tissue remained free of any signs of calcification for up to 1.5 years, while none of the other valves did, suggests that photo-oxidation is a promising method of preserving and fixing tissue for use in bioprostheses. These results suggest that photo-oxidized bioprosthetic valves may be clinically valuable and warrant further study.