[一氧化氮通过减弱特发性扩张型心肌病患者对β-肾上腺素能刺激的收缩反应来节省心肌耗氧量]

[Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy].

作者信息

Shinke T, Takaoka H, Takeuchi M, Hata K, Kawai H, Okubo H, Kijima Y, Murata T, Yokoyama M

机构信息

First Department of Internal Medicine, Kobe University School of Medicine, Kobe.

出版信息

J Cardiol. 2001 Feb;37(2):119-20.

PMID:11255696

Abstract

BACKGROUND

The results of recent studies suggest that nitric oxide (NO) synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure.

METHODS AND RESULTS

We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined left ventricular contractility (Emax, the slope of end-systolic pressure-volume relation), left ventricular external work (EW), myocardial oxygen consumption (MVO2), and mechanical efficiency (measured as EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8 +/- 0.3 micrograms.kg-1.min-1 i.v.). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 200 mumol). DOB increased Emax, EW, and MVO2 (by 77 +/- 17%, 39 +/- 5%, and 21 +/- 5%, respectively), leading to an increase in mechanical efficiency (25.4 +/- 3.1% to 29.6 +/- 4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased Emax, EW, and MVO2 (by 140 +/- 21%, 64 +/- 9%, and 35 +/- 5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3 +/- 3.3% to 29.5 +/- 4.5%) because EW and MVO2 increased in parallel.

CONCLUSIONS

These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO2 through attenuation of left ventricular contractile response to beta-adrenergic stimulation while maintaining left ventricular energy-converting efficiency.

摘要

背景

近期研究结果表明，一氧化氮（NO）合酶可能在衰竭心肌中增加，且NO可调节心肌对β-肾上腺素能刺激的收缩反应。然而，关于NO在心力衰竭患者中的生理作用的数据较少。本研究的目的是探讨NO在人类心力衰竭中对左心室对β-肾上腺素能刺激的收缩反应及相应氧消耗的作用。

方法与结果

我们研究了15例因特发性扩张型心肌病导致心力衰竭的患者（平均射血分数为0.33）。我们使用电导和冠状窦热稀释导管，在经外周静脉输注多巴酚丁胺（DOB，4.8±0.3微克·千克⁻¹·分钟⁻¹静脉注射）之前和期间，检测左心室收缩力（Emax，即收缩末期压力-容积关系的斜率）、左心室对外做功（EW）、心肌氧消耗（MVO2）和机械效率（以EW/MVO2衡量）。通过心房起搏使心率保持恒定。在冠状动脉内输注NO合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA，200微摩尔）期间，我们进行了类似的方案。DOB使Emax、EW和MVO2分别增加了77±17%、39±5%和21±5%，导致机械效率提高（从25.4±3.1%提高到29.6±4.1%）。单独使用L-NMMA并没有显著改变这些变量。尽管同时输注DOB和L-NMMA使Emax、EW和MVO2分别比单独使用DOB时增加得更多（分别增加了140±21%、64±9%和35±5%），但机械效率并没有进一步提高（从24.3±3.3%提高到29.5±4.5%），因为EW和MVO2平行增加。