Sulfinpyrazone prolongs survival and decreases platelet uptake of heart allografts

Abstract

The purpose of this study was to evaluate the potential benefit of the platelet active drug sulfinpyrazone (SPZ) on uptake of indium-III-oxine ( 111In)-labeled platelets and survival of rat heart allografts. Lewis rats bearing ACI heterotopic heart transplants were treated with SPZ in high, intermediate, or low doses. In 111-labeled platelet uptake was measured 5 days postoperatively and calculated as a ratio between the transplanted and native hearts. Left and right ventricles were measured separately. SPZ given in doses of 400 and 200 mg/kg daily significantly decreased platelet uptake in the graft and reduced the ratio of uptake between transplanted and native hearts ( P < 0.05). In animals treated with SPZ 100 mg/kg/day platelet uptake was not significantly less than that of the nontreated control animals. Survival of allografts was determined by daily palpation and compared to vehicle-treated controls. Mean graft survival was prolonged for animals treated with 100 mg/kg and 200 mg/kg daily, i.e., 19.0 ± 3.02 and 11.42 ± 1.97 days, respectively. Animals administered 400 mg/kg did not have longer graft survival than controls (6.63 ± 0.66 versus 6.31 ± 0.18 days). Most animals in the 400 mg/ kg group died as a result of adverse side effects of the drug. We conclude that SPZ in low to intermediate doses prolongs allografted heart survival. The enhanced survival in the lower dose group may in part be due to mechanisms other than platelet adhesiveness.