Microcirculatory changes during skin allograft rejection and prolongation of survival time by antiplatelet agents

The process of rejection of skin first-set-allograft transplantation was pursued by observing the microcirculation of living mice, in comparison with that of the isograft transplantation (BALB/C vs. BALB/C). The vascular connection of the skin allograft between the host (BALB/C) and graft (R III) was established on day 8, in just the same pattern as in isograft skin, but the blood flow slowed down on day 9, and the formation of microthrombi was observed in the arterioles and later in the venules and capillaries at the sites slightly inside the graft from the margin on day 10. Thereafter each small vessel of the host formed a loop and the blood flow from the host did not enter the graft. The thrombus formation was confirmed by light and electron microscopy. The importance of the thrombus formation in the rejection process was further strengthened by prolongation of the cessation of the blood flow at the boundary from day 10 to days 14-15, after daily administration from days 2 to 9 of OKY-1581 (0.4 mg/g i.p.), a selective thromboxane synthetase inhibitor, or ticlopidine (0.3 mg/10 g p.o.), an inhibitor of platelet aggregation, in combination with a subthreshold dose (0.4 mg/10 g i.p.) of azathioprine. None of these drugs alone significantly prolonged the survival time.