Immunosuppressive treatment of aortic allografts

Abstract

Immunosuppression with cyclosporine (CsA) was explored as a means of preventing arterial allograft rejection and failure. Aortic allografts across the major histocompatibility barrier were studied in Brown-Norway and Lewis inbred rats. Grafts 1 cm long were interposed into the infra-abdominal aorta of Lewis recipients; five groups included two groups of untreated isograft and allograft control animals and three groups had allograft-CsA treatment regimens. The grafts were examined at 30, 60, and 100 days for patency, aneurysmal dilation, gross structural changes, inflammatory responses, and infiltration of W3/25- and OX8-positive lymphocytes. Only three allograft controls became occluded; the rest showed significant dilation (p < 0.01), medial thinning and necrosis, intimal proliferation, and prominent cellular infiltration at 30 days. With all CsA regimens, aneurysmal dilation was significantly reduced or prevented (p < 0.01), correlating with medial smooth muscle cell preservation. Cellular infiltration was delayed by an average daily dose of 5 to 10 mg/kg subcutaneous CsA for 30 days and was suppressed at 100 days by a continuous 5 mg/kg dose every 4 days. Intimal thickening in the graft was delayed but not prevented. We conclude that a low maintenance dose of CsA provides effective immunosuppression, thereby preventing aneurysm formation, and that the potential use of arterial allografts in vascular surgery may need to be readdressed.