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新型多效血管舒张性β受体阻滞剂静脉注射卡维地洛对充血性心力衰竭的影响。

The effects of intravenous carvedilol, a new multiple action vasodilatory beta-blocker, in congestive heart failure.

作者信息

DasGupta P, Broadhurst P, Lahiri A

机构信息

Department of Cardiology, Northwick Park Hospital, Harrow, Middlesex, England.

出版信息

J Cardiovasc Pharmacol. 1991;18 Suppl 4:S12-6.

PMID:1721973
Abstract

Recent studies have shown that beta-blockers may be effective in the management of heart failure. However, negative inotropic effects of these agents may offset the beneficial properties of up-regulation of the beta-receptors and reduction in myocardial oxygen demand. Carvedilol is a new drug which possesses a balanced combination of vasodilatation and beta-blockade. Previous studies have shown that carvedilol may have beneficial effects on left ventricular function in patients with ischemic heart disease. We have performed a preliminary study to address the safety and acute effects of intravenous carvedilol in 17 patients with chronic congestive heart failure secondary to ischemic heart disease. Acute hemodynamic changes were monitored by right heart catheterization and arterial cannulation. Ejection fraction was also monitored by radionuclide ventriculography. Significant reductions in heart rate (79 +/- 14 to 72 +/- 12 beats/min, p less than 0.001) systolic and diastolic blood pressure (137 +/- 20/72 +/- 8 to 119 +/- 19/66 +/- 8 mm Hg, p less than 0.001 and p less than 0.01), systemic vascular resistance (1766 +/- 367 to 1518 +/- 377 dynes/s/cm-5/m2, p less than 0.001) and pulmonary artery wedge pressure (20 +/- 8 to 15 +/- 7 mm Hg, p less than 0.001) were observed. Ejection fraction increased significantly from 24 to 28% (p less than 0.001) but there was little change in cardiac index or stroke volume index. The peak changes occurred at 10 min and the effect on pulmonary wedge pressure was maintained up to 30 min. No adverse effects were noted. The improvements in left ventricular filling pressure and systolic function, and the reduction in sympathetic activity may combine to produce an important therapeutic advantage in congestive heart failure. Further studies with this interesting agent are recommended.

摘要

近期研究表明,β受体阻滞剂可能对心力衰竭的治疗有效。然而,这些药物的负性肌力作用可能会抵消β受体上调和心肌氧需求降低的有益特性。卡维地洛是一种兼具血管舒张和β受体阻滞作用的新药。先前的研究表明,卡维地洛可能对缺血性心脏病患者的左心室功能有有益影响。我们进行了一项初步研究,以探讨静脉注射卡维地洛对17例缺血性心脏病继发慢性充血性心力衰竭患者的安全性和急性效应。通过右心导管插入术和动脉插管监测急性血流动力学变化。还通过放射性核素心室造影监测射血分数。观察到心率(从79±14次/分钟降至72±12次/分钟,p<0.001)、收缩压和舒张压(从137±20/72±8毫米汞柱降至119±19/66±8毫米汞柱,p<0.001和p<0.01)、全身血管阻力(从1766±367达因/秒/厘米-5/平方米降至1518±377达因/秒/厘米-5/平方米,p<0.001)和肺动脉楔压(从20±8毫米汞柱降至15±7毫米汞柱,p<0.001)显著降低。射血分数从24%显著增加至28%(p<0.001),但心脏指数或每搏量指数变化不大。峰值变化出现在10分钟时,对肺楔压的影响持续至30分钟。未观察到不良反应。左心室充盈压和收缩功能的改善以及交感神经活性的降低可能共同在充血性心力衰竭中产生重要的治疗优势。建议对这种有趣的药物进行进一步研究。

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Carvedilol induces biased β1 adrenergic receptor-nitric oxide synthase 3-cyclic guanylyl monophosphate signalling to promote cardiac contractility.卡维地洛诱导偏倚的β1 肾上腺素能受体-一氧化氮合酶 3-环鸟苷酸信号促进心肌收缩力。
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Pharmacological effects of concomitant administration of beta-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise. Effects of beta-blocker combined with beta-agonist.
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An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists.α-和β-肾上腺素能受体联合拮抗剂的药效学特性及治疗潜力概述
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