| Budget Amount *help |
¥23,000,000 (Direct Cost: ¥23,000,000)
Fiscal Year 1985: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1984: ¥15,000,000 (Direct Cost: ¥15,000,000)
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| Research Abstract |
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
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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
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