The histology at various stages of acute rejection in concordant xenogeneic heart transplantation

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Abstract
In an attempt to describe early morphologic changes in heterotopic xenogeneic heart transplantation a sequential study was performed in a hamster-to-rat model. Mild morphologic changes observed after four to six h were characterized by slight interstitial edema and focal myocyte damage with fragmentation and loss of myofibrillar elements. No lymphocytic infiltration appeared. Moderate morphologic changes observed after 12-24 h were characterized by moderate interstitial edema, and the appearance of mild hemorrhage and scattered extravasated neutrophilic granulocytes. The myocardium had more widespread areas with myocyte damage, sometimes with small foci of necrotic cells and adjacent neutrophilic granulocytes and macrophages. Vascular changes with perivascular edema and swelling of the endothelium were seen and a few neutrophilic granulocytes could be found in the vessel walls. No lymphocytic infiltration appeared. Severe morphologic changes observed after 44-48 h or at the time of complete rejection were characterized by severe interstitial hemorrhage, appearance of widespread necrosis and marked vascular changes with development of leukocytoclastic-like vasculitis, possibly with thrombosis. Only a few lymphocytes appeared. The findings were essentially different from those observed in allogeneic heart transplantations, where classical first-set allograft rejection was seen. In normal donor hearts and syngeneic transplanted hearts used as controls, no significant morphologic changes were demonstrated. On the basis of this study we consider xenogeneic acute rejection to be primarily of the humoral type.