LONG TIME LOCAL IMMUNOSUPPRESSION WITH INTRAARTERIAL INFUSION OF CYCLOSPORIN IN A RAT HINDLIMB ALLOGRAFT MODEL

Guoxian Pei¹, Liangguo Guo².

¹Department of Orthopeadic Surgery, Xijing Hospital, Forth Military Medical University; ²Department of Orthopeadic Surgery, Xijing Hospital, Southern Medical University, P.R.China.

Background: Long time intra artery (i.a.) medicine infusion has been successfully used to reduce the systemic toxicity of some anticarcinogens by decreasing the whole blood concentration. For the same purpose we established a modified intra-arterial infusion model in rats to demonstrate the possibility of long time local immunosuppression.

Methods: Fully mismatched, 4- to 8-wk-old Brown Norway (RT1(n)) and Lewis (RT1(1)) rats were used as hind-limb donors and recipients, respectively. Recipients received a conditioning of antilymphocyte serum. Using a plug-able infusion mini-port subcutaneous on rats’ back, Cyclosporin A (CSA) was infused continuously into the right femoral artery at multiple doses ranging from 1.0 to 16.0 mg/kg/day. The control groups were treated with same dose of intravenous CSA, respectively. On days 7, 30, 60 and 150, the CSA concentration in peripheral vein was analyzed. Long-term survivors(>150 days) were tested for tissue CSA concentrations in skin, muscle, bone, and bone marrow samples, as well as in heart, lung, liver and kidney.

Results: The survival rates of allografts in low to moderate dose (1-8mg/kg/day) i.a. groups were significantly higher than that in same dose i.v. groups. Two-third rats treated with high dose (16mg/kg/day) intravenously died for CSA toxicity though only one animal in the i.a. group. Rats in all i.a. groups got significant higher CSA concentrations in allografts but normal level of CSA in the blood. Less accumulation of medicine was found compared to rats that received equal dose immunosuppressant intravenously.

Conclusion: Intra-arterial administration of CSA can efficiently increase the tissue concentration in allograft result in a prolonged survive of hindlimb in rats.