西地那非对5型磷酸二酯酶的急性抑制作用可增强慢性心力衰竭患者的血流介导的血管舒张功能。

Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure.

作者信息

Katz S D, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S

机构信息

Division of Circulatory Physiology, Columbia Presbyterian Medical Center, New York, New York 10032, USA.

出版信息

J Am Coll Cardiol. 2000 Sep;36(3):845-51. doi: 10.1016/s0735-1097(00)00790-7.

DOI:10.1016/s0735-1097(00)00790-7

PMID:10987609

Abstract

OBJECTIVES

To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure.

BACKGROUND

Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown.

METHODS

Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo.

RESULTS

In response to oral administration of a single dose of study drug, the change in flow-mediated vasodilation after release of 1, 3 and 5 min of arterial occlusion was significantly greater in patients receiving sildenafil 25 mg (3.3 +/- 1.9, 3.8 +/- 1.8 and 4.0 +/- 1.8%, respectively, p < 0.05) and patients receiving sildenafil 50 mg (3.7 +/- 1.3, 4.1 +/- 1.1, 3.9 +/- 1.3%, respectively, p < 0.05) than that of patients receiving placebo (0.7 +/- 1.1, 0.2 +/- 1.2, 0.6 +/- 0.8%, respectively).

CONCLUSIONS

Acute type 5 phosphodiesterase inhibition with sildenafil 25 and 50 mg increases endothelium-dependent, flow-mediated vasodilation in patients with chronic heart failure when compared with placebo.

摘要

目的

确定使用西地那非抑制5型磷酸二酯酶对慢性心力衰竭患者肱动脉血流介导的血管舒张的急性影响。

背景

心力衰竭患者内皮依赖性血流介导的血管舒张功能受损，部分原因是血管平滑肌中环磷酸鸟苷（cGMP）介导的血管舒张效应机制反应性降低。西地那非是一种特异性5型cGMP磷酸二酯酶抑制剂，抑制cGMP降解对心力衰竭患者血流介导的血管舒张的影响尚不清楚。

方法

对48例慢性心力衰竭患者进行随机、双盲分组，分别口服单剂量12.5mg、25mg或50mg西地那非或匹配的安慰剂，在给药前及给药后1小时，采用高分辨率二维超声成像测量肱动脉在短暂动脉闭塞1、3和5分钟后血流介导的血管舒张情况。

结果

口服单剂量研究药物后，接受25mg西地那非的患者（分别为3.3±1.9%、3.8±1.8%和4.0±1.8%，p<0.05）和接受50mg西地那非的患者（分别为3.7±1.3%、4.1±1.1%、3.9±1.3%，p<0.05）在动脉闭塞1、3和5分钟后血流介导的血管舒张变化显著大于接受安慰剂的患者（分别为0.7±1.1%、0.2±1.2%、0.6±0.8%）。