Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure -: Potentiation of β-adrenergic inotropic responsiveness
Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure -: Potentiation of β-adrenergic inotropic responsiveness
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DOI：
10.1161/01.cir.97.2.161
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发表时间：
1998-01-20
期刊：
影响因子：
37.8
通讯作者：
Colucci, WS
中科院分区：
文献类型：
--
作者：
Hare, JM;Givertz, MM;Colucci, WS
背景-我们以前发现，心脏一氧化氮（NO）抑制人左心室（LV）功能障碍对β-肾上腺素能刺激的正性变力反应。这种效应是心力衰竭本身特有的还是正常人心肌的普遍特征尚不清楚。因此，我们测试的假设，心脏NO的抑制增强正性肌力反应，β-肾上腺素能刺激的患者有症状的LV衰竭，但不是在受试者与正常LV function.Methods和Results-We研究了11例LV衰竭，由于特发性扩张型心肌病和7个对照组正常LV功能。β-肾上腺素能激动剂多巴酚丁胺通过外周静脉输注之前和期间同时冠状动脉内灌注乙酰胆碱，激活激动剂偶联亚型的NO合酶，和N-G-单甲基-L-精氨酸，抑制所有亚型的NO合酶。通过测量LV压力上升的峰值速率（+dP/dt）评估收缩力的变化。多巴酚丁胺使心力衰竭患者和对照组的+dP/dt分别增加40+/-6%和73+/-14%。在心力衰竭患者和对照组中，乙酰胆碱对多巴酚丁胺的+dP/dt反应的抑制程度相似（分别为-39+/-8%和-31+/-4%; P=NS）。输注N-G-单甲基-L-精氨酸使多巴酚丁胺的+dP/dt反应增强51+/-15%（与多巴酚丁胺相比，P= 0.01），但对对照组无影响（-6+/-4%; P=NS vs多巴酚丁胺; P= 0.0002，与心力衰竭患者相比）。结论-心脏NO的抑制增强了对β-肾上腺素能受体刺激在特发性扩张型心肌病心力衰竭患者中的作用，而在左室功能正常的对照受试者中则没有。
Background-We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular (LV) dysfunction. Whether this effect is specific to heart failure per se or is a generalized feature of normal human myocardium is unknown. We therefore tested the hypothesis that inhibition of cardiac NO potentiates the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure but not in subjects with normal LV function.Methods and Results-We studied 11 patients with LV failure due to idiopathic dilated cardiomyopathy and 7 control subjects with normal LV function. The beta-adrenergic agonist dobutamine was infused via a peripheral vein before and during concurrent intracoronary artery infusion of acetylcholine, which activates the agonist-coupled isoforms of NO synthase, and N-G-monomethyl-L-arginine, which inhibits all isoforms of NO synthase. Changes in contractility were assessed by measuring the peak rate of rise of LV pressure (+dP/dt). Dobutamine increased +dP/dt by 40+/-6% and 73+/-14% in patients with heart failure and control subjects, respectively. Acetylcholine inhibited the +dP/dt response to dobutamine to a similar degree in patients with heart failure and control subjects (-39+/-8% and -31+/-4%, respectively; P=NS). infusion of N-G-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51+/-15% (P=.01 versus dobutamine) in patients with heart failure but had no effect in control subjects (-6+/-4%; P=NS versus dobutamine; P=.0002 versus heart failure patients).Conclusions-Inhibition of cardiac NO augments the positive inotropic response to beta-adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.