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与地尔硫䓬不同,Ro 40-5967不会降低慢性心肌梗死大鼠的左心室收缩力。

Ro 40-5967, in contrast to diltiazem, does not reduce left ventricular contractility in rats with chronic myocardial infarction.

作者信息

Véniant M, Clozel J P, Hess P, Wolfgang R

机构信息

Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

出版信息

J Cardiovasc Pharmacol. 1991 Feb;17(2):277-84. doi: 10.1097/00005344-199102000-00014.

Abstract

Ro 40-5967 is a new calcium antagonist that binds to the same binding site as verapamil but that has been shown to have a much lesser negative inotropic effect than verapamil. The goal of the present study was to compare the effects of Ro 40-5967 and diltiazem on left ventricular contractility in vitro and in vivo in normal rats and in rats with chronic myocardial infarction induced by ligating the left coronary artery. Left ventricular contractility was assessed in vitro in isolated perfused hearts and in vivo in conscious rats by measuring left ventricular dP/dtmax + and dP/dt at P 40. In vitro, both Ro 40-5967 and diltiazem did not decrease cardiac contractility up to a dose producing complete atrioventricular block. In vivo, diltiazem decreased dP/dtmax + and dP/dt at P 40. Ro 40-5967 was less negative inotropic than diltiazem. We conclude that if these results were confirmed in clinical trials. Ro 40-5967 might be a safer drug than diltiazem, especially in patients with left ventricular dysfunction.

摘要

Ro 40 - 5967是一种新型钙拮抗剂,它与维拉帕米结合于相同的结合位点,但已证明其负性肌力作用比维拉帕米小得多。本研究的目的是比较Ro 40 - 5967和地尔硫䓬对正常大鼠以及结扎左冠状动脉诱导慢性心肌梗死大鼠的左心室收缩力的体外和体内作用。通过测量离体灌注心脏的左心室dP/dtmax +和P 40时的dP/dt在体外评估左心室收缩力,在清醒大鼠体内进行评估。在体外,高达产生完全房室传导阻滞的剂量时,Ro 40 - 5967和地尔硫䓬均未降低心脏收缩力。在体内,地尔硫䓬降低了P 40时的dP/dtmax +和dP/dt。Ro 40 - 5967的负性肌力作用比地尔硫䓬小。我们得出结论,如果这些结果在临床试验中得到证实,Ro 40 - 5967可能是比地尔硫䓬更安全的药物,尤其是在左心室功能不全的患者中。

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