EXPERIMENTAL STUDY ON PATHOGESIS OF ACUTE MYOCARDIAL INFARCTION-ROLE OF LOCAL AND NEUROHUMORAL FACTORS-

急性心肌梗死发病机制的实验研究-局部和神经体液因素的作用-

• 批准号: 04454273
• 负责人: NAKAMURA Motoomi
• 金额: $ 4.35万
• 依托单位: NAKAMURA-GAKUEN COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454273/
• 关键词: Medial necrosis; Aortic thrombosis; WHHL; Hyperlipidemia; Acute myocardial infarction; Disruption of thickened intima; Russel's viper venom; Angiotensin II; 大動脈中膜壊死; WHHL; へび毒; 動脈硬化; 心筋梗塞; 冠細小動脈硬化; 間歇的高脂血症; 細小動脈硬化; 血液凝固

Coronary angiography cannot adequately predict the site of a subsequent thrombotic occlusion following an acute myocardial infarction (AMI). In addition, the mechanisms of sudden coronary occlusion still remain completely unknown. The aim of the present study is to induce AMI experimentally by increasing blood coagulability in various types of arteriosclerotic rabbits.Thirty-nine WATANABE heritable hyperlipidemic rabbits (WHHL) with an average age of 18 months, were used in this study. Seventy-seven rabbits were fed cholesterol either intermittently or continuously for 8-12 months and 9 normal rabbits were used. To increase blood coagulability, Russel's viper venom (RVV : 150mug/kg) was administered intraperitoneally with an intravenous injection of either serotonin (100mug/kg) or angiotensin II (Ang : 20-40mug/kg) for 2 days. A typical AMI lesion (less than 48 hours old) was found in 2 out of the 9 normal rabbits, seven of 29 WHHL rabbits and none of 67 cholesterol-fed rabbits who all … More received RVV with serotonin or angiotensin. Occlusive coronary thrombosis was found in 5 of the 29 WHHL rabbits but in none of the cholesterol-fed rabbits. Only 2 of the 5 coronary thrombi were associated with coronary atherosclerosis, but neither any plaque-ruptures nor macrophage rich plaque was found at the thrombotic site. Ang (30mug/kg) promoted aortic thrombosis associated with segmental medial necrosis and a disruption of the thickened intima at the edge of the plaque in the WHHL rabbits, when compared with that of the WHHL rabbits which received RVV and serotonin (p<0.01). No close correlation between the macrophage rich plaque and aortic thrombosis was confirmed.We thus conclude that AMI lesions were rarely produced by a thrombo-embolism of the aggregated thrombi due to hypercoagulability, but not associated with plaque-rupture of the coronary atherosclerosis, while the elevation of blood pressure by angiotensin II promoted aortic thrombosis in association with medial necrosis and an intimal disruption of the thickened intima in the WHHL rabbits concerned. Less

冠状动脉造影不能充分预测急性心肌梗死（AMI）后血栓性闭塞的部位。此外，冠状动脉突然闭塞的机制仍然完全未知。本研究采用39只平均年龄18月龄的WATANABE遗传性高脂血症家兔（WHHL），通过提高不同类型动脉粥样硬化家兔的血液凝固性来诱发急性心肌梗死（AMI）。77只家兔间断或连续喂饲胆固醇8-12个月，9只正常家兔。为了增加血液凝固性，将Russel蝰蛇毒液（RVV：150 μ g/kg）与静脉内注射5-羟色胺（100 μ g/kg）或血管紧张素II（Ang：20- 40 μ g/kg）一起腹膜内施用2天。在9只正常家兔中有2只、29只WHHL家兔中有7只和67只胆固醇喂养的家兔中均未发现典型的AMI病变（小于48小时）， ...更多信息 接受了含5-羟色胺或血管紧张素的RVV。29只WHHL兔中有5只发生闭塞性冠状动脉血栓形成，但胆固醇喂养兔中无一例发生闭塞性冠状动脉血栓形成。5例冠状动脉血栓中仅2例与冠状动脉粥样硬化有关，但血栓部位未发现任何斑块破裂或富含巨噬细胞的斑块。与接受RVV和5-羟色胺的WHHL兔相比，Ang（30 μ g/kg）促进了WHHL兔主动脉血栓形成，并伴有节段性中膜坏死和斑块边缘增厚的内膜破裂（p<0.01）。富含巨噬细胞的斑块与主动脉血栓形成之间没有密切的关系，因此我们得出结论，AMI病变很少是由高凝状态引起的聚集血栓栓塞引起的，但与冠状动脉粥样硬化斑块破裂无关，而血管紧张素II引起的血压升高促进了主动脉血栓形成，与中膜坏死和增厚内膜的内膜破裂有关，关于兔子的事少

项目成果

Nakamura M.& Abe S.: "Small coronary artery sclerosis of the intermittent hypercholesterolemic rabbits ditters from that of the hereditary hypercholesterolemic rabbit." Circulation. 86 supl. I-371- (1992)

中村 M.

Nakamura M., Abe S.: "Experimental induction of acute myocardial infarction and arterial thrombosis-Angiotensin II promotes aortic thrombosis in association with medial necrosis and disruption of thickened intima in WHHL rabbit" (in preparation).

Nakamura M.、Abe S.：“急性心肌梗塞和动脉血栓形成的实验诱导——血管紧张素 II 促进 WHHL 兔的主动脉血栓形成，并与内侧坏死和增厚内膜破坏相关”（准备中）。

Koyaanagi, S.,Aoki M., Tashiro H.etal: "Prevalence and pathogenesis of silent myocardial ischemia following myocardial infaction" Jap.Circ J.58. 635-635 (1994)

Koyaanagi, S.、Aoki M.、Tashiro H.etal：“心肌梗死后无症状心肌缺血的患病率和发病机制”Jap.Circ J.58。

Koyanagi,S.,Aoki M.,Tashiro H.etal: "Prevalence and pathogenesis of silent myocardial ischemia following myoacrdial infarction" Jap.Circ J.58. 635-645 (1994)

Koyanagi,S.，Aoki M.，Tashiro H.etal：“心肌梗死后无症状心肌缺血的患病率和发病机制”Jap.Circ J.58。

Noma M.,Tomoike H., Ando H.etal: "Collateral development induced by repetitive brief coronary occlusion relates to the functional state of pre-existing collaterals." Jap.Circ J.58. 269-277 (1994)

Noma M.、Tomoike H.、Ando H.等人：“重复性短暂冠状动脉闭塞引起的侧支发育与先前存在的侧支的功能状态有关。”