内皮素-A受体阻断在起搏诱导的充血性心力衰竭进展过程中的作用。

The effects of endothelin-A receptor blockade during the progression of pacing-induced congestive heart failure.

作者信息

Saad D, Mukherjee R, Thomas P B, Iannini J P, Basler C G, Hebbar L, O S J, Moreland S, Webb M L, Powell J R, Spinale F G

机构信息

Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.

出版信息

J Am Coll Cardiol. 1998 Nov 15;32(6):1779-86. doi: 10.1016/s0735-1097(98)00439-2.

DOI:10.1016/s0735-1097(98)00439-2

PMID:9822109

Abstract

OBJECTIVES

We sought to identify the effects of endothelin (ET) subtype-A (ET(A))) receptor blockade during the development of congestive heart failure (CHF) on left ventricle (LV) function and contractility.

BACKGROUND

Congested heart failure causes increased plasma levels of ET and ET(A) receptor activation.

METHODS

Yorkshire pigs were assigned to four groups: 1) CHF: 240 beats/min for 3 weeks; n=7; 2) CHF/ET(A)-High Dose: paced for 2 weeks then ET(A) receptor blockade (BMS 193884, 50 mg/kg, b.i.d.) for the last week of pacing; n=6; 3) CHF/ET(A)-Low Dose: pacing for 2 weeks then ET(A) receptor blockade (BMS 193884, 12.5 mg/kg, b.i.d.) for the last week, n=6; and 4) CONTROL: n=8.

RESULTS

Left ventricle fractional shortening decreased with CHF compared with control (12+/-1 vs. 39+/-1%, p < 0.05) and increased in the CHF/ET(A) High and Low Dose groups (23+/-3 and 25+/-1%, p < 0.05). The LV peak wall stress and wall force increased approximately twofold with CHF and remained increased with ET(A) receptor blockade. With CHF, systemic vascular resistance increased by 120%, was normalized in the CHF/ET(A) High Dose group, and fell by 43% from CHF values in the Low Dose group (p < 0.05). Plasma catecholamines increased fourfold in the CHF group and were reduced by 48% in both CHF/ET(A) blockade groups. The LV myocyte velocity of shortening was reduced with CHF (32+/-3 vs. 54+/-3 microm/s, p < 0.05), was higher in the CHF/ET(A) High Dose group (39+/-1 microm/s, p < 0.05), and was similar to CHF values in the Low Dose group.

CONCLUSIONS

ET(A) receptor activation may contribute to the progression of LV dysfunction with CHF.

摘要

目的

我们试图确定在充血性心力衰竭（CHF）发展过程中，内皮素（ET）A 型（ET(A)）受体阻断对左心室（LV）功能和收缩性的影响。

背景

充血性心力衰竭导致血浆 ET 水平升高以及 ET(A)受体激活。

方法

将约克夏猪分为四组：1）CHF 组：以 240 次/分钟起搏 3 周；n = 7；2）CHF/ET(A)-高剂量组：起搏 2 周，然后在起搏的最后一周进行 ET(A)受体阻断（BMS 193884，50mg/kg，每日两次）；n = 6；3）CHF/ET(A)-低剂量组：起搏 2 周，然后在最后一周进行 ET(A)受体阻断（BMS 193884，12.5mg/kg，每日两次），n = 6；4）对照组：n = 8。

结果

与对照组相比，CHF 组左心室缩短分数降低（12±1%对 39±1%，p < 0.05），而 CHF/ET(A)高剂量组和低剂量组左心室缩短分数增加（分别为 23±3%和 25±1%，p < 0.05）。CHF 时左心室峰值壁应力和壁力增加约两倍，ET(A)受体阻断后仍保持升高。CHF 时，全身血管阻力增加 120%，CHF/ET(A)高剂量组恢复正常，低剂量组较 CHF 时的值下降 43%（p < 0.05）。CHF 组血浆儿茶酚胺增加四倍，两个 CHF/ET(A)阻断组均降低 48%。CHF 时左心室心肌细胞缩短速度降低（32±3 对 54±3μm/s，p < 0.05），CHF/ET(A)高剂量组较高（39±1μm/s，p < 0.05），低剂量组与 CHF 时的值相似。