Differences in the pathogenesis of first-set allograft rejection and acute xenograft rejection as determined by sequential morphologic analysis.

To examine the pathogenesis of unmodified heart xenograft and allograft rejection, a sequential morphologic analysis was undertaken. Heterotopic cardiac allografts and xenografts were performed by implanting donor hearts into the abdomen of Lewis rats. Xenograft donors were Golden Syrian hamsters and allograft donors were ACI rats. Both xenografts and allografts were excised and examined by light microscopy at specific postoperative intervals. Allograft rejection was found to be a cell-mediated process, beginning with interstitial infiltrates and perivascular cuffing, which progressed to focal myocyte necroses. Ultimately, complete replacement of the myocardium by mononuclear cells was noted in fully rejected hearts. Xenograft rejection was markedly different. Although xenograft rejection was characterized first by interstitial mononuclear cell infiltrates, unlike allografts there was only minimal progression of cellular rejection. Instead, subsequent rejection was characterized by marked interstitial edema and arteriolar vasculitis and thrombosis, leading to extensive infarcts and hemorrhage in fully rejected hearts. Fibrinoid arteriolar changes and the rapid development of edema in the absence of significant cellular infiltrate suggest that cytotoxic antibodies alter xenograft vascular permeability. These data suggest that humoral immunity is largely responsible for acute concordant xenograft rejection, whereas first-set allograft rejection is mainly a cell-mediated process.