Abstract
408 Purpose: We sought to correlate cardiac and skeletal muscle allograft rejection in a heterotopic heart transplant rat model for the following purposes: 1) to quantitate the degree and severity of skeletal muscle rejection based on the grading system for cardiac muscle rejection, and 2) to assess the feasibility of use of biopsies from simultaneously transplanted skeletal muscle for surveillance of cardiac rejection.Methods: 34 Lewis (RT11) rats underwent simultaneous heterotopic cardiac and cutaneous maximus skeletal muscle transplants. Of those, 7 rats (Group I) received syngenic grafts from Lewis donors with no immunosuppression and served as control. The remaining 25 rats received allografts from Brown Norway (RT1n) donors in two groups: Group II(n=22) received no immunosuppression, and Group III (n=5) received one week of cyclosporine. Non-immunosuppressed rats (Groups I & II) were sacrificed at days 1 through 7 after the transplant whereas immunosuppressed rats (Group III) were sacrificed at 4 weeks. Tissue sections from the grafts were graded for cellular rejection based on the grading system of the Heart Rejection Study Group (International Society for Heart and Lung Transplantation, ISHLT).Results: All group I and III grafts were functional at 7 days post-transplant with no evidence of rejection. Of group II, 2 rats showed no signs of cardiac or skeletal muscle rejection when sacrificed on day 1. All the other rats (n=20) developed graft rejection within one week after the transplant. Cellular rejection correlated grade for grade in 17/20 (85%). Of the three rats that did not show grade to grade correlation, the cardiac biopsy was interpreted as Grade IA in one case when the skeletal muscle showed no rejection. In each of the other two cases, the heart showed focal solitary lymphocytic infiltrate with myocyte replacement (Grade II), and the muscle flap showed diffuse perivascular and interstitial lymphocytic infiltrates without myocyte necrosis (Grade IB). The severity of rejection correlated in 19/20 (95%) rats: mild rejection (Grades IA, IB, II): 9/10 rats (90%); moderate (IIIA, IIIB): 6/6 (100%) and severe (IV): 4/4 (100%).Conclusion: Skeletal muscle rejection may be quantitated using the ISHLT grading system for cardiac muscle rejection. Cardiac and skeletal muscle allografts had similar pattern and severity of rejection with little grade to grade variability. The clinical implications of this correlation for surveillance of cardiac rejection warrants further investigation.
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