MONITORING EARLY CHRONIC GRAFT VASCULOPATHY AFTER HEART TRANSPLANT THROUGH SIMULTANEOUSLY TRANS-PLANTED SKELETAL MUSCLE

Abstract

424 Routine endomyocardial surveillance biopsy after cardiac transplantation carries significant risk and has poor sensitivity for diagnosing chronic graft rejection or early graft vasculopathy. We have previously shown close correlation in acute rejection findings in a rat model of simultaneous allotransplantation of heterotopic heart (HH) and cutaneous maximus muscle flap (MF). The aim of this study was to evaluate the degree of correlation of rejection patterns in a rat model of chronic rejection. METHODS: 13 Lewis rats (RT1′) underwent heterotopic heart (HH) and cutaneous maximus muscle flap (MF) allotransplants from Brown-Norway (RT1″) donors in three experimental groups: Group I (simultaneous HH and MF, n=6). Group II (HH alone, n=4) and Group III (MF alone, n=3). Allograft recipients were given cyclosporine for 10 days after transplant. Nine transplants were performed between Lewis rats and served as controls: simultaneous HH and MF (n=5). HH alone (n=3). and MF alone (n=2). Grafts were evaluated 83-93 days post-operatively by standard and immunohistochemical studies. The grade of rejection was assessed using ISHLT criteria. RESULTS: At 3 months post-transplant, Group I had 6/6 HH and 5/6 MF viable grafts. One MF was lost due to ischemic necrosis. Findings diagnostic of acute cellular rejection (Grade IIIA/IIIB) were noticed in 5/6 HH grafts and in all 5 viable MF grafts. Chronic vascular changes consistent with early graft vasculopathy and chronic rejection were present in 6/6 HH grafts and in the 5 viable MF grafts. Groups II and III examined isolated HH or MF grafts and showed similar patterns of chronic vascular rejection, vasculopathy and cellular rejection as in Group I. Rejection was identified as 'moderate' in 5 of 7 single and 5 of 6 simultaneous allografts, which showed no change in rejection severity associated with additional transplanted tissue (p=0.61). As expected, control group grafts showed no evidence of rejection, with minimal muscle atrophy. CONCLUSIONS: This rat model of simultaneous allotransplantation of HH and MF provides a method of evaluating chronic rejection. We observed a close correlation in severity of vascular changes between simultaneously transplanted HH and MF grafts. The rejection severity seen in HH and MF allografts is similar whether transplanted alone or together which may indicate the relative immunologic safety of simultaneous grafting. This new technique of evaluating vascular rejection and early graft vasculopathy may be useful in monitoring cardiac allografts for chronic rejection.