Selective aldosterone blockade suppresses atrial tachyarrhythmias in heart failure
Selective aldosterone blockade suppresses atrial tachyarrhythmias in heart failure
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DOI：
10.1111/j.1540-8167.2006.00372.x
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Stambler, BS
中科院分区：
文献类型：
--
作者：
Shroff, SC;Ryu, K;Stambler, BS
简介：肾素-血管紧张素-醛固酮系统激活可能参与充血性心力衰竭（CHF）房性心律失常的发病机制。尚未评价醛固酮阻滞剂对房性快速性心律失常的影响。本研究的目的是确定是否选择性醛固酮阻滞抑制房性快速性心律失常诱导和修改心房电和/或结构重构在犬模型的快速心室起搏（RVP）诱导的CHF.Methods和结果：狗被随机分配到治疗与口服安慰剂或依普利酮（50毫克/天），并分为四组：两个假手术（无RVP）和两个RVP组。在无RVP或RVP以230次/分沿着同时进行安慰剂或依普利酮治疗5周后，对犬进行电生理学和超声心动图研究。评估持续性房性快速性心律失常诱导（> 10分钟持续时间）、心房有效不应期（ERP）、收缩和舒张功能以及左心房和左心室（LV）腔室大小。安慰剂治疗的RVP犬发生CHF伴LV收缩和舒张功能障碍、左心房和LV扩大、心房ERP增加和可诱导的持续性房性快速性心律失常。依普利酮治疗RVP狗显着抑制持续性房性快速心律失常诱导，不均匀延长心房ERP和衰减左心室舒张功能障碍，而不改变左心房或左心室扩张或射血分数在CHF。异丙肾上腺素（2-4 μ g/min）逆转依普利酮在CHF中的心房抗心律失常和ERP延长作用。依普利酮并没有改变心房ERPs在假（无RVP）的狗没有CHF.Conclusions：依普利酮抑制诱导的持续性房性快速心律失常，选择性地抑制心房ERPs，并减弱左心室舒张期重构在RVP-induced CHF。醛固酮阻滞可能是预防CHF房性快速心律失常的一种有前途的新方法。
Introduction: Renin-angiotensin-aldosterone system activation may be involved in the pathogenesis of atrial arrhythmias in congestive heart failure (CHF). The effects of aldosterone blockade on atrial tachyarrhythmias have not been evaluated. This study's aim was to determine whether selective aldosterone blockade suppresses atrial tachyarrhythmia inducibility and modifies atrial electrical and/or structural remodeling in a canine model of rapid ventricular pacing (RVP)-induced CHF.Methods and Results: Dogs were assigned randomly to treatment with oral placebo or eplerenone (50 mg/day) and divided into four groups: two sham-operated (no RVP) and two RVP groups. After 5 weeks of no RVP or RVP at 230 beats/min along with concurrent placebo or eplerenone treatment, dogs underwent electrophysiologic and echocardiographic studies. Sustained atrial tachyarrhythmia inducibility (> 10-minute duration), atrial effective refractory periods (ERPs), systolic and diastolic function, and left atrial and left ventricular (LV) chamber sizes were assessed. Placebo-treated RVP dogs developed CHF with LV systolic and diastolic dysfunction, left atrial and LV enlargement, increased atrial ERPs, and inducible sustained atrial tachyarrhythmias. Eplerenone treatment in RVP dogs significantly suppressed sustained atrial tachyarrhythmia inducibility, nonuniformly prolonged atrial ERPs and attenuated LV diastolic dysfunction without modifying left atrial or LV dilation or ejection fractions in CHF. Isoproterenol (2-4 mu g/min) reversed eplerenone's atrial antiarrhythmic and ERP prolonging effects in CHF. Eplerenone did not alter atrial ERPs in sham (no RVP) dogs without CHF.Conclusions: Eplerenone suppresses inducibility of sustained atrial tachyarrhythmias, selectively prolongs atrial ERPs, and attenuates LV diastolic remodeling in RVP-induced CHF. Aldosterone blockade may be a promising new approach for atrial tachyarrhythmia prevention in CHF.