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PATHOGENESIS AND PATHOPHYSIOLOGY OF EXPERIMENTAL CORONARY ARTERY SPASM

实验性冠状动脉痉挛的发病机制和病理生理学

基本信息

批准号：
60570396
负责人：
TOMOIKE Hitonobu
金额：
$ 1.09万
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 (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

Although coronary artery spasm has been documented in patients with variant angina pectoris, its pathogenesis or mechanism has been debated not only in clinical observations but also in experimental studies. The goal of this study was 1) to characterize the pathophysiology of coronary spasm in atherosclerotic animals, 2) to determine angiographically the role of hypercholesterolemia or intimal thickening (geometric effects) on histamine-induced coronary spasm and 3) to elucidate the mechanism of arterial hypercontraction in vitro without influences of neural, humoral and hemodynamic factors. Under anesthetized condition, the left coronary artery of Gottingen miniature pigs was denuded regionally by a balloon catheter except 5 pigs in which coronary spasm was provoked by an intracoronary administration of histamine without denudation (group 1). Thirty one pigs were allotted to two groups for 3 months; a group fed a 2% cholesterol diet (group 2) and a group fed a regular diet (group 3). … More Histamine-induced luminal narrowing of the coronary artery at the spastic site was 75 <-!+> 4, 78 <-!+> 3 and 74 <-!+> 4% in groups 1, 2 and 3 , respectively. Phenylephrine, indomethacin or thiothromboxane <A_2> did not enhance coronary narrowing at the site with histamine-hypersensitivity. The serum cholesterol level 3 months after denudation was 222 <-!+> 27 and 55 <-!+> 6mg/dl in groups 2 and 3, respectively (p<0.01 between groups). Percent luminal reduction produced by histamine was exponentially related to the degree of the intimal thickening (r=0.92), however, the contribution of the intimal thickening on coronary narrowing via geometric effect was small and was about 7 %. These hearts were isolated, and were perfused by Krebs-Henseleit solution. Coronary artery hyperconstriction was provoked in vitro by histamine dose-dependently at the same site of spasm in vivo. The degree of luminal reduction (%) was similar angiographically to that in vivo. Accordingly, the vessel with intimal thickening may accompany functional alterations of contractile properties to autacoids in an experimental coronary spasm of Gottingen miniature pigs. Less

虽然变异性心绞痛患者有冠状动脉痉挛的记录，但其发病机制在临床观察和实验研究中都存在争议。本研究的目的是1)描述动脉粥样硬化动物冠状动脉痉挛的病理生理学特征，2)通过血管造影确定高胆固醇血症或内膜增厚（几何效应）对组胺诱导的冠状动脉痉挛的作用，3)阐明在体外不受神经、体液和血流动力学因素影响的动脉过度收缩的机制。麻醉状态下，除5头猪冠状动脉内注射组胺引起冠状动脉痉挛外，其余猪均采用球囊导管局部剥脱冠状动脉（1组）。31头猪分为两组，试验期3个月；一组喂食2%胆固醇饮食（组2）和一组喂食常规饮食（组3）. ...组胺诱导的痉挛部位冠状动脉管腔狭窄为75 <-！+> 4,78 <-！+> 3和74 <-！1、2、3组分别为+> 4%。苯肾上腺素、吲哚美辛或硫代血栓素<A_2>不能增强组胺过敏部位的冠状动脉狭窄。剥脱后3个月血清胆固醇水平222 <-！+> 27和55 <-！2组和3组间差异有统计学意义（p<0.01）。组胺产生的管腔减少百分比与内膜增厚程度呈指数相关（r=0.92），然而，内膜增厚通过几何效应对冠状动脉狭窄的贡献很小，约为7%。这些心脏被分离，用Krebs-Henseleit溶液灌注。在体外，组胺在体内痉挛的同一部位引起冠状动脉过度收缩。血管造影显示管腔缩小程度（%）与体内相似。因此，在哥廷根小型猪实验性冠状动脉痉挛中，内膜增厚的血管可能伴随着对类动脉收缩特性的功能改变。少