A controlled sequential morphologic study of hyperacute cardiac allograft rejection in the rat.

A series of heterotopic cardiac allografts from ACI strain rat donors to ACI skin-presensitized Lewis strain recipients was examined by light and electron microscopy at intervals from 1 minute to 24 hours for a sequential morphologic study of hyperacute rejection. Syngeneic Lewis hearts grafts in ACI skin-presensitized Lewis recipients provided controls. Extensive platelet aggregation throughout the vasculature of the allografts in the presence of a largely intact endothelium was the initial morphologic event, which was present by 1 minute posttransplant and absent in all syngeneic controls. This was followed by widespread endothelial damage. Endothelial damage preceded neutrophil margination and emigration in the graft. Neutrophil degranulation or evidence of phagocytosis was not observed within the 1st hour. At 6 and 24 hours, degranulated forms were common and apparent extrusion of granule contents with progressive ischemic injury. Segmental occlusion of the vasculature by platelet plugs and progressive disruption and loss of capillaries combined with an increase in permeability may result in myocardial ischemia. Neutrophil-derived agents do not appear to be of major significance in hyperacute rejection during the early posttransplant phase, but may play a role in mediating myocardial injury if the allograft survives for alonger period. However, on morphologic grounds, it is suggested that microcirculatory hypoperfusion with resultant ischemia is a major determinant of myocardial damage and graft function. No significant change was noted over the observation period in peripheral neutrophil or platelet counts when compared to syngeneic controls, and a slight reudction in specific cytotoxic antibody titer in the allografts was immediate but very transient.