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研究在透视下对小型猪进行冠状动脉内皮球囊剥脱术，饲养3个月后，冠脉内注射组胺反复诱发冠脉痉挛。为了在不受血液成分和神经控制影响的情况下评价冠脉痉挛，并定量研究组胺所致冠脉过度收缩的药理特征，分离同一心脏，在90 mm Hg恒定灌流压力下用Krebs-Henseleit液灌流。用含2.6 mM Ca~(2+)和Gt~(2+)的电解液灌流的猪心，可复制局部增强的冠脉对组胺的收缩作用。在体内和体外，对组胺反应的裸露区域的收缩在拓扑上是相同的。结论：1.冠状动脉痉挛的发病机制可能与血管内膜肥厚的血管内膜H_1受体激活引起的钙离子内流改变有关。原代培养的大鼠血管平滑肌细胞内游离钙离子浓度的变化用微量荧光法记录并负载Quin-2。重复使用去极化(100 mM K^+)和咖啡因(19 MM)后，钙离子的瞬时升高反复出现，峰值水平逐渐降低。钙释放的定量分析表明，咖啡因和去极化敏感的细胞内钙离子结合部位是相同的。

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.