The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model

Abstract

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)