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新型钙拮抗剂FR 7534、硝酸甘油和双嘧达莫对犬冠状动脉部分闭塞时局部心肌血流及心脏收缩力的比较作用

Comparative effects of a new calcium antagonist, FR 7534, nitroglycerin, and dipyridamole on regional myocardial blood flow and cardiac contractility during partial coronary artery occlusion in the dog.

作者信息

Gross G J, Warltier D C, Jolly S R, Hardman H F

出版信息

J Cardiovasc Pharmacol. 1980 Nov-Dec;2(6):797-813. doi: 10.1097/00005344-198011000-00009.

Abstract

The present study was designed to determine the effects of three different types of coronary vasodilators--FR 7534 (a new calcium antagonist), nitroglycerin, and dipyridamole--on the transmural blood flow and contractile function in the normal and ischemic myocardium of anesthetized dogs. Radioactive microspheres (15 muc) and Walton-Brodie strain gauge arches were used to measure tissue blood flow and contractile force, respectively. During 5 min intravenous infusions of nitroglycerin (5 microgram/kg/min) or dipyridamole (50 microgram/kg/min), which produced approximately 20% reductions in mean aortic pressure, blood flow and contractile force in ischemic myocardium decreased significantly. Under similar conditions, FR 7534 (10 microgram/kg/min) produced a significant decrease in ischemic contractile force, but tissue blood flow to the ischemic area did not change. In contrast, when mean aortic pressure was controlled by administration of methoxamine, nitroglycerin produced significant increases in ischemic blood flow (42%) and contractile force (47%), whereas dipyridamole produced significant decreases (41 and 32%, respectively). On the other hand, FR 7534 plus methoxamine produced a significant increase in ischemic blood flow (70%); however, ischemic contractile force did not change. These results demonstrate FR 7534 to affect the oxygen supply-demand balance in ischemic myocardium favorably by maintaining blood flow and depressing contractility during hypotension or by increasing flow during controlled systemic pressure.

摘要

本研究旨在确定三种不同类型的冠状血管扩张剂——FR 7534(一种新型钙拮抗剂)、硝酸甘油和双嘧达莫——对麻醉犬正常心肌和缺血心肌的透壁血流及收缩功能的影响。分别使用放射性微球(15μm)和沃尔顿-布罗迪应变片式传感器来测量组织血流和收缩力。在静脉输注硝酸甘油(5μg/kg/min)或双嘧达莫(50μg/kg/min)5分钟期间,平均主动脉压降低约20%,缺血心肌的血流和收缩力显著下降。在类似条件下,FR 7534(10μg/kg/min)使缺血收缩力显著降低,但缺血区域的组织血流未改变。相反,当通过给予甲氧明控制平均主动脉压时,硝酸甘油使缺血血流显著增加(42%),收缩力增加(47%),而双嘧达莫则使血流和收缩力显著降低(分别为41%和32%)。另一方面,FR 7534加甲氧明使缺血血流显著增加(70%);然而,缺血收缩力未改变。这些结果表明,FR 7534可通过在低血压时维持血流并抑制收缩力,或在控制全身压力时增加血流,从而有利地影响缺血心肌的氧供需平衡。

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