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| Cardiac Xenotransplantation Technology Provides Materials for Improved Bioprosthetic Heart Valves |
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Christopher G. McGregor1, Nermine Lila2, Michal Vlasin1, John S. Logan1, Guerard W. Byrne1; 1Surgery, Mayo Clinic, Rochester, MN; 2Cardiac Surgery, University of Paris, Paris, France Objective: Humans and Old World primates have high levels of anti-Gal antibody. Gal knockout pigs (GTKO) were produced by somatic nuclear transfer (cloning) to eliminate this dominant xeno antigen from prospective pig cardiac donors. Today's commercially available bioprosthetic heart valves (BHV), of porcine and bovine origin, retain the Gal antigen despite current processing techniques. Anti-Gal immune responses have been reported in patients after implantation of BHVs. BHV degeneration with calcification may, in part, have an immunological basis. This study tests whether binding of human anti-Gal antibody effects calcification of wild type and GTKO glutaraldehyde-fixed porcine pericardium using a standard rat implantation model. Methods: Pericardium was obtained from GTKO and wild type pigs. Expression of α-Gal was characterized by lectin GSIB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and GTKO pigs were implanted into 12-day-old Wistar rats with and without prelabeling with affinity purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by inductively coupled plasma spectroscopy. Results: The α-Gal antigen was detected in wild type but not GTKO porcine pericardium. Wild type pericardial disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared to antibody free wild type samples (111±8.4 mg/g and 74±9.6 mg/g respectively. P=0.01, mean + SEM). In the presence of anti-Gal antibody significantly greater level of calcification was detected in wild type compared to GTKO pericardium (111±8.4 mg/g and 55±11.8 mg/g respectively. P=0.005). Calcification of GTKO pericardium was not effected by the presence of anti-Gal antibody (51±9.1 mg/g and 55±11.8 mg/g). Conclusion: In this model, anti-Gal antibody accelerates calcification of wild type but not GTKO glutaraldehyde-fixed pericardium. This study suggests that preformed and induced anti-Gal antibody may contribute to calcification of currently used BHVs. GTKO pigs may become the preferred source for new potentially calcium resistant BHVs allowing greater durability and wider application of this valve type to younger patients. Back to 2010 Annual Meeting Back to Program Outline Back to Main Program |
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