IMMUNOSUPPRESSION FOR HUMAN SAPHENOUS-VEIN ALLOGRAFT BYPASS-SURGERY -A PROSPECTIVE RANDOMIZED TRIAL

Purpose: Vein allografts are an alternative bypass conduit for patient s who lack adequate autogenous vein. Animal studies have demonstrated that patency can be augmented by low-dose immunosuppression with azath ioprine. Methods: In a prospective trial, 40 patients (20 men, 20 wome n) were randomly assigned to receive (17) or to not receive (23) azath ioprine (1 mg/kg/day) after cryopreserved vein allograft bypass grafti ng. Patients had pain or tissue loss that required bypass grafting to pedal or crural outflow and lacked adequate autogenous saphenous vein. Anti-HLA antibody screens were obtained before and after surgery. Bio psies of allografts were performed at implantation and at all subseque nt opportunities. Postoperative physical and vascular laboratory exami nations occurred every 3 months. Results: During the 31-month follow-u p interval (mean, 15.7 months) there were 10 deaths (none immunosuppre ssion-related). The primary graft patency rate at 12 months was 13%, a nd the limb salvage rate was 42%. No significant difference (p > 0.05) was noted between immunosuppressed and control groups for mortality r ate, primary graft patency rate, or limb salvage rate. As a predictor of graft failure, positive preoperative anti-HLA antibody screen (8 pa tients) approached significance (p = 0.09). Of 22 explanted grafts, 13 (59%) had histologic evidence of rejection (six immunosuppressed, sev en control). Seven patients who had negative results of preoperative a nti-HLA antibody screens converted after surgery, and six patients had positive results of preoperative screens that became more strongly po sitive. Conclusion: Vein allograft failure is in part mediated by reje ction, which is not eliminated by low-dose azathioprine. Both humoral (antibody) and cellular responses to vein allografts develop. The poor patency rates of vein allograft bypass grafts may be improved by more potent immunosuppression as well as improvement in allograft procurem ent, preservation, and matching.