Shinke T, Takaoka H, Takeuchi M, Hata K, Kawai H, Okubo H, Kijima Y, Murata T, Yokoyama M
First Department of Internal Medicine Kobe University School of Medicine, Kobe, Japan.
Circulation. 2000 Apr 25;101(16):1925-30. doi: 10.1161/01.cir.101.16.1925.
The results of recent studies suggest that 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 (LV) contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure.
We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E(max), the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVO(2)), and mechanical efficiency (measured as EW/MVO(2)) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4. 8+/-0.3 microg. kg(-1). min(-1) IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 200 micromol). DOB increased E(max), EW, and MVO(2) (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 E(max), EW, and MVO(2) (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 MVO(2) increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO(2) through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.
近期研究结果提示，一氧化氮合酶可能在衰竭心肌中增加，且一氧化氮可调节心肌对β-肾上腺素能刺激的收缩反应。然而，关于一氧化氮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一氧化氮在人类心力衰竭中对左心室（LV）对β-肾上腺素能刺激的收缩反应及相应氧消耗的作用。
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±0.3μg·kg⁻¹·min⁻¹静脉注射）之前及期间，检测左心室收缩性（E(max)，即收缩末期压力-容积关系的斜率）、左心室外部功（EW）、心肌氧消耗（MVO₂）及机械效率（以EW/MVO₂衡量）。通过心房起搏使心率保持恒定。在冠状动脉内输注一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸（L-NMMA，200μmol）期间，我们执行了类似的方案。DOB使E(max)、EW和MVO₂增加（分别增加77±17%、39±5%和21±5%），导致机械效率增加（从25.4±3.1%增至29.6±4.1%）。单独使用L-NMMA并未显著改变这些变量。尽管同时输注DOB和L-NMMA使E(max)、EW和MVO₂增加（分别增加140±21%、64±9%和35±5%）的幅度大于单独使用DOB，但机械效率并未进一步增加（从24.3±3.3%增至29.5±4.5%），因为EW和MVO₂平行增加。结论 - 这些数据提示，在特发性扩张型心肌病患者中，内源性一氧化氮通过减弱左心室对β-肾上腺素能刺激的收缩反应来节省MVO₂，同时维持左心室能量转换效率。
