Effects of complement suppression on xenograft survival in hyperacute rejection

To examine the significance of complement in discordant cardiac xenograft rejection, morphological changes in the rejection reaction were investigated following administration of FUT-175 (FUT), an anticomplement reagent. Guinea pigs were the cardiac donors, and Wistar rats were the recipients. Four groups of rats were constituted as follows: Group 0 was the control group. FUT of 40 mg/kg was injected intraperitoneally in group I. It was followed by continuous intravenous infusion (20 and 40 mg/kg/hr) in groups II and III. In one series, the effects of FUT on complement suppression was examined. In the FUT groups of rats (groups I to III), the serum levels of CH50 and ACH50 were measured at 0, 1, 2 and 4 hr following injection of FUT. In the second series of rats with identical treatments, the graft heart beating time following cardiac transplantation was measured. Cardiac transplantation into untreated rats was also performed as a control (group 0). In another series, the graft hearts in the FUT groups were extracted after 15, 30, 60 and 90 min of coronary reperfusion for morphological examination with scanning electron microscopy. The complement levels decreased significantly in the FUT-treated rats in a dose-dependent manner. Although the graft heart beating times in the FUT-treated groups were significantly longer than in group 0 (103, 106, and 112 min versus 14.7 min, p < 0.01), there was no significant difference in the graft heart beating time or in the morphological changes among the three FUT groups. Our results suggest the presence of factors other than complements contribute to the cardiac xenograft rejection.