EXPERIMENTS IN CARDIAC XENOTRANSPLANTATION - RESPONSE TO INTRATHYMIC XENOGENEIC CELLS AND INTRAVENOUS COBRA VENOM FACTOR

Permanent tolerance to an experimental cardiac allograft can be achiev ed by pretransplantation intrathymic inoculation of donor-specific lym phoid cells. We studied the effects of intrathymic inoculation of xeno geneic cells and intravenous cobra venom factor in a rodent model of c ardiac xenotransplantation. Lewis rats underwent intraabdominal hetero topic heart transplantation with Syrian hamster donors. In untreated a nimals, mean graft survival time was 3 days. Five rats had 1 nd of ant ilymphocyte serum administered intraperitoneally. One day later, 2.5 x 10(7) hamster spleen cells were inoculated into the thymus under dire ct vision. Twenty-one days after antilymphocyte serum was given, heter otopic heart transplantation with a hamster donor was carried out. In all cases, rejection was accelerated and occurred between 20 minutes a nd 1 day after transplantation. Mean graft survival time was 5.2 hours (p < 0.0001 versus control). Six animals treated with antilymphocyte serum and intrathymic xenogeneic cells had 0.5 ml of cobra venom facto r, a complement antagonist, administered intravenously 3 hours before transplantation and every other day thereafter. Mean graft survival wa s 3 days, which was not different from the response of naive animals. Animals treated with antilymphocyte serum only had no prolongation of graft survival (mean survival time 3 days, p = not significant). Anima ls treated with cobra venom factor alone (n = 5) before transplantatio n and on alternate days subsequently had mild graft prolongation with a mean survival time of 4 days (p = 0.0133). In contrast to experiment al allograft models, intrathymic inoculation of xenogeneic cells produ ces hyperacute rejection in these naturally concordant species. The ad ministration of cobra venom factor abrogates the hyperacute response, but the combination of cobra venom factor and intrathymic inoculation does not produce long-term graft survival.