Effect of in Vitro Irradiation of Donor Larynges on Cyclosporine Requirements and Rejection Rates in Rat Laryngeal Transplantation

Abstract

Total lymphoid irradiation is an acknowledged adjunctive immunosuppressant in whole organ transplantation in humans and animals. Local irradiation administered for a similar purpose is at best controversial. We evaluated in vitro donor larynx irradiation immediately preceding laryngeal transplantation as an immunomodulator. Each donor larynx was pretreated with 7.34 Gy of radiation in vitro. After transplantation, cyclosporine was administered in doses of 5 mg/kg per day, 2.5 mg/kg per day, and 1 mg/kg per day for trial lengths of 15 days and 30 days. Each of these 6 groups consisted of 10 rats per group. Earlier data have shown cyclosporine dosed at 5 mg/kg per day, without irradiation, administered for 1 month to have varied efficacy. Established histologic criteria were used to determine rejection patterns. All recipient rats survived the 15-day and 30-day trials. In all 10 rats receiving 5 mg/kg per day of cyclosporine for 15 days, the harvested transplanted larynges were viable without evidence of meaningful rejection (mild rejection). In 9 of the 10 rats receiving 5 mg/kg per day of cyclosporine for 30 days, the transplanted larynges displayed no meaningful rejection (mild rejection). In 9 of the 10 rats receiving 2.5 mg/kg per day of cyclosporine for 15 days, the transplanted larynges displayed no meaningful rejection (mild rejection). One rat receiving 2.5 mg/kg per day of cyclosporine for 15 days had a transplanted larynx that displayed moderate rejection. In all 10 rats receiving 2.5 mg/kg per day of cyclosporine for 30 days, the transplanted larynges displayed no meaningful rejection (mild rejection). At 15 days, 5 rats treated with 1 mg/kg per day of cyclosporine displayed mild rejection, 2 displayed moderate rejection, 2 displayed advanced to moderate rejection, and 1 displayed severe rejection. At 30 days, 4 rats treated with 1 mg/kg per day of cyclosporine displayed moderate rejection, 2 displayed advanced to moderate rejection, and 4 displayed severe rejection. We conclude that pretransplantation in vitro irradiation of donor larynges has immunomodulatory effects, allowing reduced cyclosporine immunosuppression with less rejection.