Sulfinpyrazone prolongs survival and decreases platelet uptake of heart allografts

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, intermed...

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Veröffentlicht in:The Journal of surgical research 1989-06, Vol.46 (6), p.549-552
Hauptverfasser: Bergsland, J., Carroll, M., Feldman, M.J., Wright, J.R., Mentzer, R.M., Carr, E.A.
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container_end_page 552
container_issue 6
container_start_page 549
container_title The Journal of surgical research
container_volume 46
creator Bergsland, J.
Carroll, M.
Feldman, M.J.
Wright, J.R.
Mentzer, R.M.
Carr, E.A.
description 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.
doi_str_mv 10.1016/0022-4804(89)90018-8
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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 &lt; 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. 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subjects Animals
Blood Platelets - metabolism
Cyclosporins - pharmacology
Graft Survival - drug effects
Heart Transplantation
Male
Prednisolone - pharmacology
Rats
Rats, Inbred Lew
Sulfinpyrazone - pharmacology
Transplantation, Homologous
Transplantation, Isogeneic
title Sulfinpyrazone prolongs survival and decreases platelet uptake of heart allografts
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