Prolongation of survival of guinea pig heart grafts in cobra venom factor-treated rats by splenectomy : no additional effect of cyclosporine

In recent years, the study of xenotransplantation has met with promising results. Long-term survival of concordant grafts has been reported in small animal models as well as in monkeys. In contrast, the survival times of discordant vascularized grafts are still poor. The reported survival of a pig heart in a monkey of 22 days by Alexandre et al. in 1989 is the longest survival reported today. The results obtained in the guinea pig (GP*) to rat combination underscore the hardness of the discordant problem. The longest survival time of GP hearts in rat recipients reported today is 7 days. This was achieved by treating the rats with cobra venom factor in combination with splenectomy (Spx) and deoxyspergualin. It was argued that the additional effect of deoxyspergualin could be ascribed to inhibition of B cells producing anti-GP antibodies. We were interested to know whether partial antibody depletion in complement-deficient rats indeed results in prolongation of GP hearts. Pretransplant Spx was performed to reduce antibody titers and cobra venom factor (CVF) to deplete complement activity. We were further interested to see whether T cells were involved in the rejection of GP hearts in the absence of hyperacute rejection. Although it is generally accepted that T cells are of no importance in hyperacute rejection, their role has not been established in the rejection of discordant grafts in a situation where hyperacute rejection is precluded. Therefore, we have studied the role of T cells in the rejection of GP heart grafts in complement-depleted, splenectomized rats by treating these rats additionally with cyclosporine (CsA).