Relationship between the evolution of coronary artery spasm and atherosclerosis and related basic studies on the mechanisms of coronary spasm

1. 实验动物模型冠状动脉痉挛的机制采用透视法对小型猪进行冠状动脉内皮球囊剥脱，饲养实验室饲料3个月，冠状动脉内注射组胺反复引起冠状动脉痉挛。为了评估不受血液成分和神经控制影响的冠状动脉痉挛，并定量观察组胺诱导的冠状动脉过度收缩的药物生理特征，我们分离同一心脏，在90 mmHg的恒定灌注压力下灌注Krebs-Henseleit溶液。在离体猪心脏中灌注含有2.6 mM Ca^<2+>的电解质溶液，可重现冠状动脉对组胺的局部增强收缩。在体内和体外，对组胺反应的剥落区收缩在拓扑结构上是相同的。在h_1受体刺激下，血管平滑肌内Ca^<2+>的内流发生改变，伴有内膜增厚，这可能是冠状动脉痉挛的一种可能机制。用微荧光法记录了大鼠血管平滑肌细胞原代培养和负载quin-2后胞浆游离钙浓度的变化。钙的短暂升高反复出现在重复去极化（100 mM K^+）和咖啡因（19 mM）应用的反应中，峰值水平逐渐降低。对释放钙的定量分析表明，对咖啡因和去极化敏感的细胞内钙异位是相同的。

1. Mechanisms of Coronary Arterial Spasm in Experimental Animal Model Endothelial balloon denudation of the coronary artery was performed under fluoroscopy in miniature pigs and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of histamine-induced coronary hyperconstriction, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mmHg. Focally potentiated constriction of the coronary artery to histamine was reproducible in isolated pig hearts perfused with electrolyte solution containing 2.6 mM Ca^<2+>. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. Alterations in the influx of Ca^<2+> in the presence of H_1-receptor stiumulation in vascular smooth muscle of the vessel with intimal thickening was suggested as a plausible mechanism of coronary spasm.2. Cellular Mechanisms of Ca^<2+> Handling in Cultured Smooth muscle Cell Changes in the concentration of cytosolic free calcium were recorded microfluorometrically in rat vascular smooth muscle cells in primary culture and loaded with quin-2. Transient elevations of calcium repeatedly appeared in response to both repetitive depolarization (100 mM K^+) and caffeine (19 mM) applications with progressive reductions in peak levels. Quantitative analysis of released calcium suggested that caffeine- and depolarization-sensitive intracellular calcium strage sites is identical.