[Fine-structural analysis of hyper-acute rejection in cardiac xenotransplantation]

Hyper-acute rejection after cardiac xenotransplantation has been extensively studied, but its morphological changes have not been adequately elucidated yet. We investigated the morphological changes in two kinds of cardiac xenotransplantation models, guinea pig hearts in rats and hamster hearts in sensitized rats, in terms of histology, immunohistochemistry. TdT-mediated dUTP nick-end labeling (TUNEL) and ultrastructure. Four guinea pig hearts were heterotopically transplanted to rats and four hamster hearts to sensitized rats by the modified technique of Ono and Lindsey. In the hamster-to-rat model, the rats were treated with a hamster skin tissue at two weeks before transplantation. Rejection of the grafts was diagnosed from cessation of the graft heart contraction. Immunohistochemically, C3 was deposited along all vessels including coronary vessels, arterioles, venules and capillaries, and IgM was deposited along major vessels in the guinea pig grafts; it was vice versa in the hamster grafts. In the guinea pig grafts, TUNEL showed positive staining in endothelial cells and myocytes, whereas no positive signal was shown in the rejected hamster hearts. Transmission electron microscopy revealed platelet aggregations in the vessels of guinea pig-to-rat and hamster-to-sensitized rat cardiac xenografts. In the guinea pig-to-rat cardiac xenografts, capillary walls were thin with a high electron density and the number of pinocytotic vesicles was reduced. Also several nuclei of the endothelial cells showed pyknosis and some nuclei were fragmented. On the other hand, these findings were not typical in the hamster-to-sensitized rat cardiac xenografts. In conclusion, this study revealed thromboembolism of capillaries and impairment of the endothelial cells in the hyper-acutely rejecting cardiac xenografts. Apoptosis of myocytes and endothelial cells was shown to be involved only in the hyper-acutely rejecting guinea pig-to-rat cardiac xenografts. These results indicated variability in hyper-acute rejection.