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J Thorac Cardiovasc Surg 2000;119:1216-1220
© 2000 The American Association for Thoracic Surgery

SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE

FRESH PORCINE CARDIAC VALVES ARE NOT REJECTED IN PRIMATES

Raymond H. Chen, MD, PhDa, Alexander Kadner, MDa, Richard N. Mitchell, MD, PhDb, David H. Adams, MDa

From the Departments of Surgerya and Pathology,b Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass.

Dr Chen is an American College of Surgeons Research Scholar 1998-00 and recipient of National Institutes of Health Individual National Research Service Award (NRSA) 1F32HL0996601. This work is supported by a Nextran, Inc, sponsored research grant. Primate quarantine work was supported by the New England Primate Research Center grant P51RR00168-37.

Address for reprints: David H. Adams, MD, Division of Cardiac Surgery, Brigham & Women’s Hospital, 15 Francis St, Boston, MA 02115 (E-mail: dadams{at}partners.org ).

Objective: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose {alpha}-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected.
Methods: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose {alpha}-1,3-galactose, primate immunoglobulin M, and membrane attack complex.
Results: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose {alpha}-1,3-galactose antigen, galactose {alpha}-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M– and membrane attack complex–mediated damage.
Conclusions: The absence of galactose {alpha}-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted.




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