A NEW RAT INFECTION-HEART TRANSPLANT MODEL - EFFECT OF INFECTION ON GRAFT-SURVIVAL STUDIES

Considerable progress has been made in survival rates of heart transpl ant recipients; however, infections continue to be a major cause of de ath after transplantation. Although infection itself appears to cause immunologic suppression in some nontransplantation studies, the lack o f an infection-transplant animal model has limited further investigati on of this observation. We evaluated the utility of a heterotopic rat infection heart-transplant model by studying the effect of infection a nd limited administration of two immunosuppressive agents, cyclosporin e and FK506, on allograft rejection and survival. Lewis rats received ACI heart allografts, and intraperitoneal infection was induced by cec al ligation. Infection was confirmed by blood and ascitic fluid cultur es. Results showed that graft survival was slightly, but significantly , higher (p < 0.05) in group II (transplantation with infection) when compared to the control group I (transplantation only). Histologic rej ection scores were less (p < 0.05) in group II 6 days after transplant ation. The second phase of the study compared the effect of infection after transplantation in rats given a 1-week course of cyclosporine or FK506, which were discontinued after the induction of infection. Alth ough the cyclosporine group had prolonged survival when compared to th e FK506 group (p < 0.05), the respective infection groups receiving im munosuppression revealed no significant difference in allograft surviv al or histologic rejection scores when compared to the control groups. In this preliminary study, infection without immunosuppression result ed in a slight, but statistically significant, increase in allograft s urvival and reduced acute cellular rejection. In those groups receivin g immunosuppressive agents, no additive immunosuppressive effect was a ttributable to bacterial infection. Further studies in this model inve stigating differential cytokine expression between infection and rejec tion are warranted.