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急性或慢性冠状动脉闭塞远端的心肌灌注:地尔硫䓬和硝苯地平的作用。

Myocardial perfusion distal to an acute or chronic coronary artery occlusion: effects of diltiazem and nifedipine.

作者信息

Zyvoloski M G, Brooks H L, Gross G J, Warltier D C

出版信息

J Pharmacol Exp Ther. 1982 Aug;222(2):494-500.

PMID:7097568
Abstract

The effect of two slow channel calcium antagonists, diltiazem and nifedipine, on perfusion of normal and ischemic myocardium was studied in anesthetized dogs with acute or chronic (ameroid constrictor) left anterior descending coronary artery occlusion. Diltiazem (15 and 30 micrograms/mkg/min i.v.) produced significant (P less than .05) and dose-related decreases in heart rate and mean aortic blood pressure and an increase in left circumflex coronary blood flow. Nifedipine (1 and 3 micrograms/kg/min i.v.) also produced a significant reduction in mean aortic blood pressure and an increase in left circumflex coronary artery blood flow; however, no change in heart rate was observed. Both diltiazem and nifedipine increased myocardial blood flow in the normal zone in dogs with acute or chronic coronary artery occlusion, and this effect was potentiated when aortic blood pressure was prevented from decreasing. Following a reduction in aortic blood pressure no significant change in ischemic zone perfusion was observed after diltiazem in dogs with an acute occlusion; flow was significantly increased in dogs with a chronic occlusion. In both models, diltiazem produced a redistribution of ischemic zone blood flow to the subendocardium. In dogs with acute or chronic occlusion nifedipine produce an increase in ischemic zone flow primarily to the subepicardium. The effect of each agent on tissue perfusion was enhanced in the chronic occlusion model. These data demonstrate marked differences in effects of diltiazem and nifedipine on hemodynamics and regional myocardial perfusion and stress the importance of experimental models in evaluating the effects of the calcium antagonists on coronary collateral blood flow.

摘要

在患有急性或慢性(阿梅罗氏缩窄器)左前降支冠状动脉闭塞的麻醉犬中,研究了两种慢通道钙拮抗剂地尔硫䓬和硝苯地平对正常和缺血心肌灌注的影响。地尔硫䓬(静脉注射15和30微克/千克/分钟)可使心率和平均主动脉血压显著(P<0.05)且呈剂量依赖性降低,并使左旋冠状动脉血流量增加。硝苯地平(静脉注射1和3微克/千克/分钟)也可使平均主动脉血压显著降低,并使左旋冠状动脉血流量增加;然而,未观察到心率变化。地尔硫䓬和硝苯地平均可增加急性或慢性冠状动脉闭塞犬正常区域的心肌血流量,当防止主动脉血压降低时,这种作用会增强。在急性闭塞犬中,主动脉血压降低后,地尔硫䓬治疗后缺血区域灌注无显著变化;在慢性闭塞犬中,血流量显著增加。在两种模型中,地尔硫䓬均可使缺血区域的血流重新分布至心内膜下。在急性或慢性闭塞犬中,硝苯地平主要使缺血区域的心外膜下血流量增加。在慢性闭塞模型中,每种药物对组织灌注的作用均增强。这些数据表明地尔硫䓬和硝苯地平对血流动力学和局部心肌灌注的影响存在显著差异,并强调了实验模型在评估钙拮抗剂对冠状动脉侧支血流影响方面的重要性。

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