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Pathogenesis and prevention of myocardial injury induced by coronary artery spasm

冠状动脉痉挛心肌损伤的发病机制及预防

基本信息

批准号：
59440044
负责人：
NAKAMURA Motoomi
金额：
$ 14.72万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1985
项目状态：
已结题

项目摘要

1. Characteristics of Coronary Artery Spasm in Our Swine Model: The role of prostanoids and leukotriene (LT) in a swine model of coronary artery spasm was examined. Thirty four miniature pigs underwent endothelial denudation of the left coronary artery followed by high cholesterol feeding. Three months after the denudation, when coronary artery spasm was repeatedly provoked along the denuded portion of the coronary artery by histamine, the role of prostanoids and LTs on coronary artery spasm was examined in 18 and 16 pigs, respectively. ( <i> ) Intracoronary administration of thiothromboxane <A_2> , 200 <micro> g, a stable Tx <A_2> analog, failed to provoke coronary artery spasm, but nonselectively constricted the coronary artery by 33%. Continuous intravenous infusion of prostacyclin, 50 ng/kg per min, failed to prevent histamine-induced coronary artery spasm, yet the spasm was all but prevented by intravenous pretreatment with diphenhydramine at a dose of 1 mg/kg. Thus, in this swine … More model, prostanoids may not play a primary role in the occurrence of coronary artery spasm. ( <ii> ) Intracoronary administration of <LTC_4> and <LTD_4> in doses of 1 and 10 <micro> g caused ECG-ST elevation along with delayed filling of the coronary artery angiographically. Nevertheless, those LTs did not provoke augmented vasconstriction in any site of the epicardial coronary arteries. FPL-55712, 0.1 mg/kg by which LT-induced myocardial ischemia was completely abolished, did not prevent histamine-induced coronary artery spasm. Accordingly, in our swine model of coronary spasm, LTs constricted coronary arteries at the level of small vessels and rendered the perfused myocardium ischemic, yet they did not play a primary role in the provocation of histamine-induced spasm.2. Feasibility of in vitro Studies of Coronary Spasm: We tested whether augmented vasoconstriction is reproducible by histamine in vitro similar to in vivo with regard to the degree and location of the spasm in miniature pigs, after endothelial denudation and cholesterol feeding for 3 months. Coronary artery spasm was reproduced in isolated hearts under constant pressure perfusion with Krebs-Henseleit solution. Absence of <Ca^(++)> in the perfused sobution prevented the histamine-induced spasm.3. Cell Biological Analysis of Smooth Muscle Contraction: ( <i> ) Receptor characteristics of the cell membrane extracts derived from the porcine coronary artery and aorta were examined with regard to alpha, beta and <H_1> receptors using a radioligand binding technique. ( <ii> ) The new method for determining cytosolic <Ca^(++)> kinetics in the cultured smooth muscle cell was established using micro-fluorometric measurement of Quin II loaded physiologically. Less

1.我们的猪模型中冠状动脉痉挛的特征：检查前列腺素类和白三烯（LT）在猪冠状动脉痉挛模型中的作用。对34只小型猪进行左冠状动脉内皮剥脱术，然后喂饲高胆固醇饲料。剥脱3个月后，当冠状动脉痉挛反复引起沿着冠状动脉的剥脱部分的组胺，前列腺素类和LT的冠状动脉痉挛的作用进行了检查，分别在18和16只猪。（<i>）冠状动脉内注射硫代血栓烷<A_2>（200 <micro>g，一种稳定的Tx<A_2>类似物）未能引起冠状动脉痉挛，但非选择性地使冠状动脉收缩33%。连续静脉输注前列环素，50 ng/kg/min，未能防止组胺诱导的冠状动脉痉挛，但痉挛，但预防静脉注射苯海拉明，剂量为1 mg/kg。因此，在这头猪 ...更多信息模型中，前列腺素类可能在冠状动脉痉挛的发生中不起主要作用。（<ii>）冠状动脉内给<LTC_4>药<LTD_4>1和10 <micro>g可导致ECG-ST段沿着升高，并伴有冠状动脉血管造影充盈延迟。然而，这些LT并未引起心外膜冠状动脉任何部位的血管收缩增强。FPL-55712（0.1 mg/kg）完全消除了LT诱导的心肌缺血，但不能预防组胺诱导的冠状动脉痉挛。因此，在我们的猪冠状动脉痉挛模型中，LT在小血管水平收缩冠状动脉并使灌注心肌缺血，但它们在组胺诱导的痉挛的激发中没有发挥主要作用。冠状动脉痉挛体外研究的可行性：我们测试了在内皮剥脱和胆固醇喂养3个月后，在小型猪中痉挛的程度和位置方面，组胺在体外与体内相似是否可重现血管收缩增强。冠状动脉痉挛复制在离体心脏恒压灌注与Krebs-Henseleit溶液。灌流液中缺乏<Ca^（++）>可阻止组胺引起的痉挛.平滑肌收缩的细胞生物学分析：（<i>）使用放射性配体结合技术检查了猪冠状动脉和主动脉细胞膜提取物的α、β和受体的受体特性<H_1>。（<ii>）建立了生理负载的Quin Ⅱ微荧光法测定培养的平滑肌细胞胞浆Ca ~（++）动力学的新方法。少