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卡维地洛(金络)可减小犬急性心肌梗死模型中的梗死面积。

Carvedilol (Kredex) reduces infarct size in a canine model of acute myocardial infarction.

作者信息

Hamburger S A, Barone F C, Feuerstein G Z, Ruffolo R R

机构信息

Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.

出版信息

Pharmacology. 1991;43(3):113-20. doi: 10.1159/000138836.

Abstract

Carvedilol (Kredex) is a multiple action, antihypertensive agent that may also prove to be useful in the treatment of angina and congestive heart failure. Carvedilol combines in one molecule both beta-adrenoceptor blocking and vasodilating activities. Inasmuch as beta-adrenoceptor blocking agents are known to be cardioprotective and thereby reduce infarct size, it is logical to assume that carvedilol, likewise, would possess this desirable activity. Furthermore, the additional vasodilating activity of carvedilol could contribute to further reductions in infarct size by reducing myocardial work (and therefore myocardial oxygen demand) through reductions in both afterload and myocardial wall tension. As such, we have investigated the ability of carvedilol to reduce infarct size in a canine model of acute myocardial infarction. Carvedilol (1 mg/kg i.v.) or its vehicle, dimethylformamide, were administered 15 min before left circumflex coronary artery (LCX) occlusion. Following 1 h of LCX occlusion, dogs were reperfused through a critical stenosis and then allowed to recover for 24 h. Carvedilol-treated animals exhibited a 78% reduction in infarct size compared to vehicle controls, such that the percentage of the left ventricle infarcted was reduced significantly from 16.2 +/- 4.1% in control animals to 3.6 +/- 1.3% in animals treated with carvedilol (p = 0.017, n = 6). Stained tissue sections of the left ventricle were photographed, digitized and color-enhanced using an Image Analysis Computer System, and three-dimensional reconstruction of the left ventricle, including the infarcted areas, was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

卡维地洛(金络)是一种具有多种作用的抗高血压药物,在治疗心绞痛和充血性心力衰竭方面可能也有效果。卡维地洛在一个分子中兼具β -肾上腺素能受体阻断和血管舒张活性。鉴于已知β -肾上腺素能受体阻断剂具有心脏保护作用,从而能减小梗死面积,所以合理推测卡维地洛同样具有这种有益活性。此外,卡维地洛额外的血管舒张活性可通过降低后负荷和心肌壁张力来减少心肌做功(进而降低心肌需氧量),有助于进一步减小梗死面积。因此,我们研究了卡维地洛在犬急性心肌梗死模型中减小梗死面积的能力。在左旋冠状动脉(LCX)闭塞前15分钟静脉注射卡维地洛(1毫克/千克)或其溶媒二甲基甲酰胺。LCX闭塞1小时后,犬通过严重狭窄处进行再灌注,然后恢复观察24小时。与溶媒对照组相比,卡维地洛治疗的动物梗死面积减少了78%,左心室梗死百分比从对照动物的16.2±4.1%显著降低至卡维地洛治疗动物的3.6±1.3%(p = 0.017,n = 6)。对左心室的染色组织切片进行拍照、数字化处理,并使用图像分析计算机系统进行颜色增强,然后对包括梗死区域在内的左心室进行三维重建。(摘要截短于250字)

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