EFFECT OF GRAFT PRESERVATION AND IGM DEPLETION ON GUINEA-PIG TO RAT CARDIAC XENOGRAFT SURVIVAL

Background. Heterotopic guinea pig (GP) cardiac xenografts (XG) are hy peracutely rejected within minutes when transplanted into rats. Method s. In this GP to rat cardiac XG model, we studied the effect on graft survival of a short cold preservation time (1 hr at 4 degrees C) in th e presence or absence of rat anti-GP IgM preformed antibodies. The com plete depletion of circulating IgM was obtained by two intraperitoneal injections of anti-rat IgM monoclonal antibody (MARM-4) on preoperati ve days -3 and -1. Results. When the GP cardiac XG was cold preserved for 1 hr before transplantation, the mean graft survival time (MST) wa s 13.5+/-2.8 min, whereas without previous cold preservation, the MST was significantly prolonged to 51.5+/-12.3 min (P<0.001). Interestingl y, the complete depletion of preformed circulating IgM before grafting significantly prolonged the MST of a cold-preserved XG to 37.1+/-11.3 min in comparison with a nondepleted recipient of a cold-preserved XG (P<0.02), but did not prolong the graft survival of a XG that was not cold preserved (42.5+/-14.1 min). To assess the effect of cold preser vation and/or ischemia reperfusion, we intravenously injected a supero xide-dismutase mimetic (EUK-134) just before transplantation of a cold -preserved XG;. This antioxidant regimen improved the MST from 13.5+/- 2.8 min to 35.3+/-7.3 min (P<0.001). These results clearly suggested t hat either preservation lesions or preformed IgM are capable of accele rating the loss of the cardiac graft function, but also that the prese nce of preformed IgM seems to be especially deleterious when the cardi ac XG has previously been ischemically injured. Analyzing the histolog ical data, we also observed that the prompt cessation of cardiac funct ion seen in cold-preserved grafts was uniformly associated with massiv e interstitial hemorrhage, thereby suggesting a particular susceptibil ity of the CP cardiac XG to cold preservation. To assess the effect of preservation on the GP cardiac function in a nonimmunological model, we performed syngeneic GP cardiac grafts and found that 1 hr of cold p reservation provoked massive interstitial hemorrhage capable of prompt ly inducing the cessation of the heartbeat. Conclusions. Overall, this study demonstrated that both ischemic lesions and immunological proce sses might induce the cessation of cardiac graft function in the GP to rat model and this cessation of graft function is probably often misi nterpreted as a XG rejection only.