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两种二氢吡啶类钙拮抗剂对急性心肌缺血时冠状动脉侧支血流影响的比较。

Comparison of two dihydropyridine calcium antagonists on coronary collateral blood flow in acute myocardial ischemia.

作者信息

Jolly S R, Hardman H F, Gross G J

出版信息

J Pharmacol Exp Ther. 1981 Apr;217(1):20-5.

PMID:7205654
Abstract

Effects of two dihydropyridine calcium antagonists on regional myocardial blood flow produced by acute ligation of the left anterior descending coronary artery were examined in the pentobarbital-anesthetized open-chest dog. Equivalent hypotensive doses of nifedipine (1.25 and 2.5 microgram/kg/min) and FR 7534 (5 and 10 micrograms/kg/min) produced similar decreases in mean arterial pressure and myocardial oxygen consumption and increases in coronary blood flow, dp/dt and contractile force in the intact nonischemic dog heart. Heart rate was unaffected. Nifedipine was 4 times as potent as FR 7534. Effects on ischemic myocardial blood flow measured with radioactive microspheres were examined with the same doses and also at controlled mean arterial pressure by use of methoxamine. Despite significant hypotension, nifedipine maintained and FR 7534 increased ischemic blood flow. When perfusion pressure was controlled, both compounds produced significant increases in transmural blood flow to the ischemic region. The increase produced by FR 7534 was significantly greater. Both nifedipine and, to a lesser extent, FR 7534 decreased the subendocardial to subepicardial blood flow ratio in the nonischemic myocardium without altering that of the ischemic myocardium. Drug-induced increases in ischemic blood flow were positively correlated with initial flow rate. The results indicate that both dihydropyridine calcium antagonists are capable of improving the oxygen supply-demand relationship during ischemia by reducing overall myocardial oxygen demand by increasing collateral blood flow.

摘要

在戊巴比妥麻醉的开胸犬中,研究了两种二氢吡啶类钙拮抗剂对急性结扎左前降支冠状动脉所产生的局部心肌血流的影响。等效降压剂量的硝苯地平(1.25和2.5微克/千克/分钟)和FR 7534(5和10微克/千克/分钟)在完整的非缺血犬心脏中产生了相似的平均动脉压降低和心肌氧耗量降低,以及冠状动脉血流量、dp/dt和收缩力增加。心率未受影响。硝苯地平的效力是FR 7534的4倍。用相同剂量并通过使用甲氧明控制平均动脉压,研究了对用放射性微球测量的缺血心肌血流的影响。尽管有明显的低血压,硝苯地平维持且FR 7534增加了缺血血流量。当灌注压得到控制时,两种化合物均使缺血区域的透壁血流量显著增加。FR 7534产生的增加显著更大。硝苯地平和在较小程度上FR 7534均降低了非缺血心肌中的心内膜下与心外膜下血流比值,而未改变缺血心肌的该比值。药物诱导的缺血血流量增加与初始流速呈正相关。结果表明,两种二氢吡啶类钙拮抗剂均能够通过增加侧支血流量来降低整体心肌氧需求,从而改善缺血期间的氧供需关系。

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