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J Thorac Cardiovasc Surg 1998;115:118-127
© 1998 Mosby, Inc.


SURGERY FOR CONGENITAL HEART DISEASE

Pathology Of Explanted Cryopreserved Allograft Heart Valves: Comparison With Aortic Valves From Orthotopic Heart Transplants

Richard N. Mitchell, MD, PhDa, Richard A. Jonas, MDb, Frederick J. Schoen, MD, PhDa

From the Department of Pathology,a Brigham and Women's Hospital, Department of Cardiovascular Surgery,b Children's Hospital, and the Departments of Pathologya and Surgery,b Harvard Medical School, Boston, Mass.

Received for publication March 6, 1997; revisions requested May 13, 1997; revisions received June 24, 1997; accepted for publication August 18, 1997. Address for reprints: Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.

Objective: We sought to determine the morphology, mechanisms of deterioration, cellular viability, extracellular matrix integrity, and the role of immune responses in the dysfunction of cryopreserved aortic and pulmonic valve allografts.
Methods: We studied 33 explanted left-sided (n = 20) or right-sided (n = 13) cryopreserved human allograft heart valves explanted several hours to 9 years after operation, 14 nonimplanted allografts, and 16 aortic valves removed from transplanted allograft hearts 2 days to 4 years after operation. Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies.
Results: Allografts implanted for more than 1 day had progressive collagen hyalinization and loss of normal structural complexity and cellularity, including endothelium and deep connective tissue cells. Inflammatory cells were generally minimal or absent in the allografts. Transmission electron microscopy of long-term cryopreserved allograft valves revealed no viable cells, focal calcification centered around dead cell remnants, and distorted but preserved collagen. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including endothelium and abundant deep connective tissue cells; inflammatory infiltrates were generally mild and of no apparent deleterious consequence, including valves from patients who died of fatal rejection.
Conclusions: Cryopreserved allografts are morphologically nonviable; their collagen is flattened but largely preserved. They are unlikely to grow, remodel, or exhibit active metabolic functions, and their usual degeneration cannot be attributed to immunologic responses. In contrast, aortic valves of transplanted hearts maintain near-normal overall architecture and cellularity and do not show apparent immunologic injury, even in the setting of fatal myocardial parenchymal rejection or graft arteriosclerosis.




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