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J Thorac Cardiovasc Surg 2001;122:310-317
© 2001 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease (ACD)

Prevention of allograft heart valve failure in a rat model

From the Departments of Surgery,^a Pathology,^b and Microbiology and Immunology,^c Dalhousie University, Halifax, Nova Scotia, Canada.

Supported by the Toronto Hospital for Sick Children Research Foundation.

Received for publication June 7, 2000. Revisions requested Sept 5, 2000; revisions received Sept 28, 2000. Accepted for publication Oct 16, 2000. Address for reprints: David Burns Ross, MD, IWK Grace Health Centre, 5850/5980 University Ave, Halifax, Nova Scotia, Canada, B3J 3G9 (E-mail: dross{at}iwkgrace.ns.ca).

Abstract

Objective: Allograft heart valves are commonly used in cardiac surgery. Despite mounting evidence that these valves are immunogenic, leading to premature failure, current clinical practice does not attempt to minimize or control such a response. The objective of this study was to evaluate immune modulatory approaches to ameliorate allograft valve failure in a rat model.
Method: Aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 32). There were 4 transplant groups: syngeneic grafts (Lewis to Lewis), untreated allografts (Brown Norway to Lewis), allograft recipients treated with cyclosporine (INN: ciclosporin) (10 mg/kg per day for 7 or 28 days), and allograft recipients treated with anti-4 integrin and anti-ß2 integrin monoclonal antibodies for 7 days. At 7 and 28 days the valves were examined for structural integrity and cellular infiltration.
Results: Both cyclosporine and anti-4/ß2 integrin treatment resulted in significant reduction in leaflet infiltration by macrophages (ED1⁺), T cells (CD3⁺), and CD8⁺ T cells at 7 days with preservation of structural integrity when compared with control allografts. Twenty-eight days after implantation, daily treatment with cyclosporine preserved leaflet structural integrity and inhibited cellular infiltration. However, a short course of cyclosporine (7 days) failed to prevent destruction of the valves at 28 days.
Conclusions: Immune modulatory approaches aimed at T-cell activation or trafficking decrease leaflet cellular infiltration and prevent allograft valve structural failure. However, short-course therapy does not appear to be sufficient and must be maintained to allow long-term preservation of leaflet structural integrity (28 days).

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