Rejection pattern of simultaneously transplanted cardiac and skeletal muscle grafts in a rat model

We studied the correlation of cardiac and skeletal muscle allograft rejection in a rat model to assess the feasibility of using biopsies from simultaneously transplanted skeletal muscle for surveillance of cardiac graft rejection.

Thirty Lewis rats (RT1l)) underwent simultaneous heterotopic heart and cutaneous maximus flap (HHCM) allotransplant. Seven recipient rats (control) received syngeneic HHCM grafts from Lewis donors while the remaining 23 (study group) received HHCM grafts from Brown Norway (RT1n) donors. Control rats were sacrificed after 7 days while rats in the study group were serially sacrificed at days 1-7 after transplantation. No immunosuppression was given. The tissue sections from the HHCM grafts were assessed for acute rejection based on the grading system adopted by the International Society for Heart and Lung Transplantation.

As expected, all the control rats had no evidence of rejection. One study animal developed an infection in the skeletal muscle allograft and was excluded. Two study animals had no evidence of rejection when sacrificed 1 day after transplant. The remaining 20 rats developed acute cellular rejection in their graft(s). Upon comparison of acute cellular rejection between the heterotopic heart and the cutaneous maximus flap grafts, rejection correlated grade for grade in 75% (15 of 20 rats). All five rats that did not have identical grades of rejection had mild rejection (grades IA, IB and II). Presence or absence of rejection, therefore, correlated in 20/22 rats: 15/20 rats with cardiac rejection and 2/2 rats without cardiac rejection.

Cardiac and skeletal muscle allografts have similar pattern of rejection with little grade to grade variability. The clinical implications for surveillance of cardiac rejection warrants further investigation.