An ultrastructural analysis of concordant and discordant cardiac xenografts in unmodified recipients. A sequential study in rodents with special reference to endothelial cell changes in the microvascular system.

Ultrastructural changes in endothelial cells in a hamster-to-rat and guinea pig-to-rat heart transplantation model are described. In the hamster-to-rat model, changes were minimal with an increase in cytoplasmic vesicles 4-6 h after transplantation. 16-24 h after transplantation larger vesicles appeared and the basement and cell membranes were less well defined. 42-48 h after transplantation the changes had progressed with destruction of cell membranes and the appearance of extravasated changes had progressed with destruction of cell membranes and the appearance of extravasated erythrocytes. At the time of complete rejection, changes had further progressed with widespread endothelial cell destruction and infiltration of neutrophilic granulocytes and macrophages, and large amounts of fibrin were present. In the guinea pig-to-rat model, changes were characterized by the appearance of platelets in close contact with the endothelium of the capillaries 1-3 min after transplantation. 4-6 min after transplantation the basement membranes as well as the cell membranes were affected with indistinct borders and interruption. Occasionally fusion of platelets and endothelial cell membranes was demonstrated. In the grafts examined 7-9 min after transplantation, changes had further progressed. Massive aggregation of platelets now appeared in relation to remnants of endothelial cells. Signs of microvascular damage appeared in both models, but with different morphology. In hamster grafts, endothelial cell activation is indicated by gradual changes in the cell membranes resulting in vascular damage and infiltration of the grafts by macrophages and neutrophilic granulocytes. In the guinea pig grafts, activation of endothelial cells results in platelet aggregation, formation of microthrombi, and subsequent tissue damage. Even though antibody and complement are involved in both types of rejection the basic mechanisms are different.