| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Shousuke KYUSHU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (30038723)
TANIYAMA Takuro KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (70117167)
AKATA Takashi KYUSHU UNIVERSITY,FACULTY OF MEDICINE,INSTRUCTOR, 医学部, 助手
吉武 潤一 九州大学, 医学部, 教授 (10041386)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
It is quite an important issue to prevent thrombus formation,i.e. to maitain anticoagulation in the clinical management of an extracorporeal circulation, such as a cardiopulmonary bypass in the cardovascular surgery. Although a surface-heparinized circuit, a newly developed thromboresistant material, has been reported to be effective to maintain anticoagulation during the extracorporeal circulation, it has not yet been introduced into the routine clinical practice. Until now, systemic administration of heparin has long been used to prevent thrombus formation in the circuit in the management of the extracorporeal circulation. Various adverse responses, such as hypotension, pulmonary hypertension, or thrombocytopenia, have been reported during the protamine reversal of heparin anticoagulation at the end of the extracorporeal circulation. Although such adverse hemodynamic effects of protamine can be critical in some patients, their precise mechanisms have not yet been fully elucidated. We
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, therefore, investigated the effects of protamine on vascular smooth muscle and endothelium, employing isometric tension recording methods. It was then found that only protamine itself, but not a heparin-protamine complex, has inhibitory actions on both vascular smooth muscle and endothelium. It was also suggested that protamine exert its inhibitory effects on vascular smooth muscle probably by stimulating the endothelium to release EDRF,by inhibiting the Ca^<2+> influx into the smooth muscle cell, and by inhibiting the Ca^<2+> release from the intracellular store of smooth muscle cell. Furthermore, it was suggested from the experiments with heparin that the inhibitory effects of protamine on vascular smooth muscle and endothelium are probably due to its positive charge, and that protamine presumably exert its direct vasodilating action without entering the smooth muscle cell. Previous reports have shown that free protamine exists in the blood during the heparin reversal besides a heparin-protamine complex. Putting the above findings together, it is suggested that the observed in vitro inhibitory effects of protamine on vascular smooth muscle and endothelium may partly explain the adverse hemodynamic effects of protamine occurred during the heparin reversal, and that the minimum possible amount of protamine should be administered slowly to reverse the heparin anticoagulation. Finally, our present data strongly suggest the importance of the determination of the amount of protamine required for the precise reversal of heparin anticoagulation, and the necessity of the early introduction of the "heparin-surfaced" circuit, which does not require the administration of protamine at the end of the extracorporeal circulation, into the clinical setting. Less
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