CARDIOVASCULAR ENGINEERING Journal for Extracorporeal Circulation, Assist Devices,Transplantation and Artificial Organs
	Volume 2, 1997, No 1

Whole Organ Vascularized Cluster Heart-Thymus Allografting: Experiences with a Novel Experimental Model

M. D’Silva, E. Antoniou, A. J. Howie, P. Bonnet, P. McMaster

Abstract:
Background: Previous work from this laboratory employing a model of heart aorta transplantation demonstrated the disparity in onset and degree of acute rejection in these organs. The purpose of this report was to develop an experimental cluster model of thymus plus heart and trachea to: study the course and sequence of acute rejection in the different organs of the cluster, determine whether heart allograft survival improves after the cotransplantation of the thymus and apply the cluster model in studies using immunosuppression. Methods: Four studies were performed using DA (RTAa), Lewis (RT11) (LEW) and PVG (RT1c) rats. Study I described the development of the cluster model employing syngeneic or allogeneic combinations. Study 2 determined whether thymus was rejected earlier than the heart and trachea in DA X LEW allografts. Study 3 compared the mean rejection times for isolated heart versus cluster grafts in three strain combinations. Study 4 assessed the response of cluster grafts under immunosuppressive treatment (leflunomide-10 mg/kg and mycophenolate mofetil-30 mg/kg) that proved optimal for isolated heart allografts. Graft survival and histology was obtained and analyzed. Results: The cluster transplant model was technically feasible, the dominant reaction after grafting being acute rejection. Rejection of the thymus preceded that of the heart clinically although there was a disparity between clinical and histological endpoints for rejection in these organs. Ciliary epithelium of the trachea and the mucosa of the esophagus were the primary targets of acute rejection as opposed to subjacent layers in both these organs. Heart allograft survival was responder-status dependent, statistically prolonged only in LEW recipients of DA clusters. Leflunomide and mycophenolate mofetil expressed different effects on cardiac graft survival in low- versus high-responder strain combinations. Conclusion: The cluster model of heart-thymus transplantation represents a valuable tool to study immune mediated events in allorejection. The model not only raises the possibility to evaluate the conditions where a large lymphoid load is either sensitizing or tolerizing to the recipients of such grafts, but also the operational cellular and subcellular mechanisms behind such processes.

Keywords:
rat, vascularized transplant, thymus transplantation, novel model, allograft, heart, tracheal graft, cluster grafting, immunosuppression, leflunomide, mycophenolate mofetil, experimental model

Address for Correspondence:

Reference:
(CVE. 1997; 2 (1): 65-74)

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