Project/Area Number |
63480231
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
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Research Institution | Kyushu University |
Principal Investigator |
TOMOIKE Hitonobu KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90112333)
|
Co-Investigator(Kenkyū-buntansha) |
KOYANAGI Samon KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90128017)
|
Project Period (FY) |
1988 – 1989
|
Project Status |
Completed (Fiscal Year 1989)
|
Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | CORONARY SPASM / SEROTONIN / X-IRRADIATION / MINIATURE PIG / ARTERIOSCLEROSIS / HYPERVENTILATION / ALKALOSIS / CORONARY ANGIOGRAPHY / 動脈硬化 / 高コレステロール血症 / 冠動脈造影 / 心筋虚血 / ヒスタミン |
Research Abstract |
Activation of coronary spasm Advanced atherosclerotic lesions were produced along the left coronary artery following repeated endothelial denudation by a balloon catheter and X-ray irradiation in Gottingen miniature pigs under (1) hypocholesterolemia and (2) hypercholesterolemia induced by diet containing 2 % cholesterol and sodium cholate. To elucidate the role of X-ray irradiation in augmented constriction to vasoactive agents, X-ray irradiation was repeated twice with the absence of intimal injury. Responses of the coronary artery to vasoactive agents were evaluated in situ angiographically as changes in luminal narrowing. Three months after mechanical injury of the intima along the left circumflex or left anterior descending coronary artery, intracoronary injection of serotonin or histamine constricted more the injured site than the contralateral intact site. Five months after denudation, coronary segments denuded and X-ray irradiated constricted more severely to serotonin than the intact site. Thus, we were able to reduce the threshold for spasm and to augment the maximal responses to serotonin. Such augmentation was significantly attenuated by intravenous pretreatment with ketanserin. Accordingly, serotonin-2 receptor function may be altered by X-ray irradiation. Two months after X-ray irradiation in cases not denuded, serotonin in a dose of 10 mug/kg constricted the intact and irradiated sites by 26<plus-minus>3 % and 45<plus-minus>2 %, respectively (p<0.01 between sites). Increased intimal thickening was noted histologically along the X-ray irradiated s Namely, X-ray irradiation per se augments both the atherosclerotic process and the responsiveness of the vessel to serotonin. Under respiratory or metabolic alkalosis, serotonin-induced hyperconstriction at the X-ray irradiated site increased from 45% to 76 % (p<0.01). Thus, alkalosis activates the responsiveness of the arteriosclerotic vessel to a spasmogenic agents.
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