EVALUATION OF 99mTc PYROPHOSPHATE TO DIAGNOSE ACUTE CARDIAC REJECTION IN THE RAT WITH STUDIES ON THE EFFECT OF CYCLOSPORINE

Abstract

Uptake of 99mTc pyrophosphate (PYP) has been shown to be a sensitive and specific indicator of ischemia myocardial injury. We investigated the uptake of 99mTc PYP during acute cardiac rejection in an experimental model of heterotopic transplantation in the rat. The model allowed comparison of uptake of PYP between the transplanted and the recipient's native heart, and the results were corrected for weight and expressed as a ratio: Transplanted/Native. Four groups of ratio were studied: Group 1 (N = 6) was between animals of isogeneic strain and the ratio of uptake was 1.85 ± 0.9 (M ± SD) which was significantly different from the ratio of 3.23 ± 0.96 in Group 2 (N = 11) in which transplants were between non-isogeneic animals (P<0.01). Group 3 (N = 7) were non-isogeneic animals treated with Cyclosporine 10 mg/Kg/day and the ratio 2.14 ± 0.5 was not different from Group 1, but was statistically different from Group 2 (P< 0.01). In contrast the ratio of uptake between non-isogeneic animals treated with subtherapeutic doses of Cyclosporine (1mg/Kg/day) Group 4 (N = 4) was 2.81 ± 0.6 which was not different from Group 2. In groups 1, 2 and 3 there was correlation between the histology of the transplanted hearts graded 1 to 5 blindly according to the severity of rejection and the uptake of 99mTc PYP. 99mTc PYP can therefore be used to diagnose cardiac rejection in a rat model, and the results correlate well with the severity of rejection as assessed histologically.