Project/Area Number |
63440037
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Research Category |
Grant-in-Aid for General Scientific Research (A)
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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 |
NAKAMURA Motoomi Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (60037322)
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Co-Investigator(Kenkyū-buntansha) |
山元 寅男 九州大学, 医学部, 教授 (80037324)
SUNAGAWA Kenji Kyushu University, Faculty of Medicine, Lecturer, 医学部, 助手 (50163043)
TOMOIKE Hitonobu Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (90112333)
KANAIDE Hideo Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (80038851)
TAKESHITA Akira Kyushu University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30038814)
居石 克夫 九州大学, 医学部, 教授 (70108710)
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Project Period (FY) |
1988 – 1989
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Project Status |
Completed (Fiscal Year 1989)
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Budget Amount *help |
¥28,400,000 (Direct Cost: ¥28,400,000)
Fiscal Year 1989: ¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 1988: ¥16,100,000 (Direct Cost: ¥16,100,000)
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Keywords | CORONARY ARTERY SPASM / MYOCARDIAL INFARCTION / SEROTONIN / INTRAMURAL HEMORRHAGE / ARTERIOSCLEROSIS / PTCA / ENDOTHELIAL CELL / EDRF / 冠動脈攣縮 / 冠動脈硬化とその進展 / 粥種内出血 / X線照射 / 血管内皮細胞 / 中膜平滑筋 |
Research Abstract |
1. Spontaneous Coronary Constriction Following Mechanical Denudation of the Coronary Artery Mechanisms of spontaneous coronary constriction following balloon injury were studied in situ angiographically. Forty six Gottingen miniature pigs were fed cholesterol rich diet for a month and were randomly allotted to 3 groups; 18 pigs in group I were given 500 units heparin intravenously, 7 in group II both 500 units heparin and 1 mg/kg ketanserin and 21 in group III 3000 units heparin. After these pretreatments, the left anterior descending and/or circumflex coronary arteries were mechanically denuded by a 2F embolectomy catheter. Spontaneous coronary constriction was noted in pigs in group I at the area denuded, which was at its peak level 6 minutes after the injury and was reverted to the control state within 30 minutes. The maximum level of coronary constriction was significantly attenuated from 56<plus-minus>5% in group I to 26<plus-minus>7% and 30<plus-minus>5% in groups II and III, res
… More
pectively. These results suggest the critical role of the platelet aggregation at the denuded area for the genesis of spontaneous coronary constri 2. Pathogenetic Effects of Coronary Spasm on Progression of Stenosis, Intramural Hemorrhage and/or Acute Myocardial Infarction The role of coronary spasm in the progression of organic coronary stenosis and/or the evolution of acute myocardial infarction was studied in 20 Gottingen miniature pigs fed cholesterol rich diet for 5 months. A branch of the left coronary artery was denuded twice 4 and 5 weeks and were X-irradiated twice 2 and 3 months after the cholesterol feeding. Two months after the 2nd X-irradiation, pigs were randomly allotted to 2 types of provocation of coronary spasm. In 10 pigs in group A, abrupt onset of severe coronary spasm was provoked by 5 intracoronary injections of 10 mug/kg serotonin every 5 minutes. The extent of coronary constriction at the denuded sites was 87<plus-minus>4, 89<plus-minus>5 and 89<plus-minus>5% at 3, 18 and 28 minutes. In group B, stepwise increases of coronary constriction were produced by increasing doses of serotonin from 0.1 to 10 mug/kg serotonin. The extent of coronary constriction was 27<plus-minus>6, 43<plus-minus>5, 57<plus-minus>3, and 85<plus-minus>5 % at 3, 8, 13, and 18 min. The sustained level of coronary constriction was maintained for 25 minutes in 4 of 10 pigs by 5 repetitive injections of 10 mug/kg serotonin (group B1). In other 6 pigs as group B2, sustained constriction was maintained for 120 minutes by 24 repeated injections of 10 mug/kg serotonin. Urokinase was given 600,000units intravenously to pigs in group B2. Intramural hemorrhage was noted at the spastic site in 9 pigs in group A and 3 in group B (p<0.01). Progression of coronary stenosis was confirmed angiographically or histologically in 7 pigs, which was related to the presence of intramural hemorrhage. Acute myocardial infarction was provoked in 5 pigs in group B2, despite the concomitant treatment with a thrombolytic agent. These results suggest that 1) the faster the acceleration of spasm is provoked, the more frequent the occurrence of intramural hemorrhage is noted, 2) intramural hemorrhage augments the extent coronary stenosis and 3) prolonged coronary spasm results in evolution of acute myocardi Less
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