Pathogenesis and prevention of myocardial injury induced by coronary artery spasm

1. 猪冠状动脉痉挛的特点：研究了前列腺素和白三烯（LT）在猪冠状动脉痉挛模型中的作用。34头小型猪接受左冠状动脉内皮剥脱，然后高胆固醇喂养。剥脱后3个月，当组胺沿着冠状动脉剥脱部分反复引发冠状动脉痉挛时，分别在18头和16头猪中检测前列腺素和LTs对冠状动脉痉挛的作用。（<i>）在冠状动脉内给予硫代血栓素<A_2>, 200 <micro> g，一种稳定的Tx <A_2>类似物，没有引起冠状动脉痉挛，但非选择性地收缩冠状动脉33%。连续静脉输注前列环素（50ng /kg / min）不能预防组胺诱导的冠状动脉痉挛，而静脉注射剂量为1mg /kg的苯海拉明预处理几乎可以预防冠状动脉痉挛。因此，在猪…More模型中，前列腺素可能在冠状动脉痉挛的发生中不起主要作用。冠状动脉内给予<LTC_4>和<LTD_4>，剂量分别为1和10 <micro> g，可引起ECG-ST升高，同时冠状动脉造影充盈延迟。然而，这些LTs并没有引起心外膜冠状动脉任何部位的血管收缩增强。0.1 mg/kg的FPL-55712完全消除了lt诱导的心肌缺血，但对组胺诱导的冠状动脉痉挛没有预防作用。因此，在我们的猪冠状动脉痉挛模型中，LTs在小血管水平上收缩冠状动脉并使灌注的心肌缺血，但它们在组胺诱导的痉挛的诱发中并不起主要作用。体外研究冠状动脉痉挛的可行性：我们测试了在内皮剥脱和胆固醇喂养3个月后，在小型猪痉挛的程度和位置方面，组胺是否可以在体外复制增强的血管收缩，与体内相似。用Krebs-Henseleit溶液恒压灌注的离体心脏再现冠状动脉痉挛。2 .灌注液中缺乏<Ca^(++)>可阻止组胺诱导的痉挛。平滑肌收缩的细胞生物学分析：采用放射配体结合技术检测猪冠状动脉和主动脉细胞膜提取物的α、β和<H_1>受体特征。（<ii>）建立了平滑肌细胞胞浆<Ca^(++)>动力学测定的新方法。少

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