The effects of combined versus selective adrenergic blockade on left ventricular and systemic hemodynamics, myocardial substrate preference, and regional perfusion in conscious dogs with dilated cardiomyopathy.
The effects of combined versus selective adrenergic blockade on left ventricular and systemic hemodynamics, myocardial substrate preference, and regional perfusion in conscious dogs with dilated cardiomyopathy.
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联合与选择性肾上腺素能阻滞对患有扩张型心肌病的清醒犬的左心室和全身血流动力学、心肌底物偏好和局部灌注的影响。
DOI：
10.1016/j.jacc.2005.11.082
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发表时间：
2006
影响因子：
24
通讯作者：
Shannon,RichardP
中科院分区：
文献类型：
--
作者：
Nikolaidis,LazarosA;Poornima,Indu;Parikh,Pratik;Magovern,Megan;Shen,You-Tang;Shannon,RichardP
由于慢性交感神经兴奋的副作用是由所有三种肾上腺素能受体亚型（β1，β2，α1）介导的，我们研究了标准剂量卡维地洛和琥珀酸美托洛尔（美托洛尔控释/缓释[CR/XL]）对血流动力学，心肌代谢和局部器官灌注的影响。即使在卡维地洛或美托洛尔欧洲试验（COMET）之后，一种药物是否优于另一种药物仍然存在争议。同样地，相对差异的机制基础是不完全understood.MethodsThirty-three有意识的，慢性仪器狗起搏诱导（240分钟-1 4周）扩张型心肌病（DCM）随机卡维地洛（25毫克，每日两次，Coreg，葛兰素史克，三角研究，北卡罗来纳州）或琥珀酸美托洛尔（100毫克，每日一次，Toprol XL，阿斯利康，特拉华州威尔明顿）。在治疗前和治疗3天后测量左心室和全身血流动力学、心肌底物摄取和去甲肾上腺素溢出。区域（肾，肝，骨骼肌）的血流量进行了测量，使用中子活化micropheres.ResultsBoth代理商有可比的心率的影响。然而，卡维地洛治疗的狗表现出显着更大的增加，每搏输出量和心输出量，并降低左心室舒张末期压和全身血管阻力。卡维地洛增加肾、肝和骨骼肌血流量。卡维地洛增加心肌葡萄糖摄取，抑制去甲肾上腺素和胰高血糖素。卡维地洛拮抗外源性去甲肾上腺素的反应在更大程度上比美托洛尔CR/XL。ConclusionsAt剂量诱导可比的心率降低，短期治疗卡维地洛有上级的血流动力学和代谢的影响相比，美托洛尔CR/XL。这些数据表明，在DCM中阻断所有三种肾上腺素能受体亚型具有重要优势。
ObjectivesGiven that adverse effects of chronic sympathetic activation are mediated by all three adrenergic receptor subtypes (β1, β2, α1), we examined the effects of standard doses of carvedilol and metoprolol succinate (metoprolol controlled release/extended release [CR/XL]) on hemodynamics, myocardial metabolism, and regional organ perfusion.BackgroundBoth β1selective and combined adrenergic blockade reduce morbidity and mortality in heart failure. Whether there are advantages of one class over the other remains controversial, even in the wake of the Carvedilol Or Metoprolol European Trial (COMET). Similarly, the mechanistic basis for the relative differences is incompletely understood.MethodsThirty-three conscious, chronically instrumented dogs with pacing-induced (240 min−1for 4 weeks) dilated cardiomyopathy (DCM) were randomized to carvedilol (25 mg twice daily, Coreg, Glaxo Smith Kline, Research Triangle, North Carolina) or metoprolol succinate (100 mg qd, Toprol XL, Astra Zeneca, Wilmington, Delaware). Left ventricular and systemic hemodynamics, myocardial substrate uptake, and norepinephrine spillover were measured before and after three days of treatment. Regional (renal, hepatic, skeletal muscle) blood flows were measured using neutron-activated microspheres.ResultsBoth agents had comparable heart rate effects. However, carvedilol-treated dogs showed significantly greater increases in stroke volume and cardiac output and decreases in left ventricular end-diastolic pressure and systemic vascular resistance. Carvedilol increased renal, hepatic, and skeletal muscle blood flow. Carvedilol increased myocardial glucose uptake and suppressed norepinephrine and glucagon. Carvedilol antagonized the response to exogenous norepinephrine to a greater extent than metoprolol CR/XL.ConclusionsAt doses inducing comparable heart rate reductions, short-term treatment with carvedilol had superior hemodynamic and metabolic effects compared with metoprolol CR/XL. These data suggest important advantages of blocking all three adrenergic receptor subtypes in DCM.