Prolonged survival of orthotopically transplanted heart xenograft in infant baboons

Abstract

Orthotopic concordant xenotransplantation in a juvenile primate model was examined. Eighteen donor rhesus monkeys weighing 2.4 to 3.8 kg (mean 2.9 kg) were matched with juvenile baboons, aged 9 to 19 months (mean 12.7 months) and weighing 3.2 to 4.8 kg (mean 3.9 kg), using ABH blood type and mixed lymphocyte culture. Rhesus monkey hearts were orthotopically transplanted without immunosuppression into six control baboons (group I). In five baboons (group II), 4 mg/kg per day of antilymphocyte globulin was administered for 3 days before the operation and 5 days after the operation. Splenectomy was also performed, and 18 mg/kg per day of FK 506 was administered orally. Intravenous methotrexate, methylprednisolone, or both were used as rescue therapy. Seven baboons (group III) received the same immunosuppression as those in group II, but an intravenous dose of methotrexate (0.1 to 5 mg) was given twice weekly to suppress the proliferative response as monitored by in vitro immunologic assays. Baboons in group I had a mean survival of 8 days; all died as a result of classic cellular rejection. Baboons in group II had a mean survival of 48.4 days (p < 0.05 versus group I). Two died during rescue therapy for rejection, and three died of cytomegalovirus infection. Two group II baboons showed mild rejection at autopsy. Baboons in group III had a mean survival of 127 days, and one baboon was still alive after 286 days. Two died of cytomegalovirus infection, one of toxoplasmosis, one of Klebsiella pneumoniae, one of massive micropulmonary embolism, one of renal failure aggravated by ganciclovir. Only two of the baboons that died showed rejection (estimated as mild) at autopsy. The baboon still alive at 286 days had no rejection on myocardial biopsy on the two hundred forty-fourth postoperative day. FK 506 coupled with low-dose maintenance methotrexate and splenectomy has produced prolonged host survival in this xenotransplantation model. Results suggest that concordant xenotransplantation would be a suitable biologic bridge to allotransplantation.