Shroff Sunil C, Ryu Kyungmoo, Martovitz Nichole L, Hoit Brian D, Stambler Bruce S
Department of Medicine/Cardiology, University Hospitals of Cleveland, Cleveland, Ohio, USA.
J Cardiovasc Electrophysiol. 2006 May;17(5):534-41. doi: 10.1111/j.1540-8167.2006.00372.x.
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.
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 microg/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.
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.
肾素 - 血管紧张素 - 醛固酮系统激活可能参与了充血性心力衰竭（CHF）时房性心律失常的发病机制。醛固酮阻断对房性快速心律失常的影响尚未得到评估。本研究的目的是确定在快速心室起搏（RVP）诱导的CHF犬模型中，选择性醛固酮阻断是否能抑制房性快速心律失常的诱发，并改变心房的电和/或结构重塑。
将犬随机分为口服安慰剂或依普利酮（50毫克/天）治疗组，并分为四组：两组假手术组（无RVP）和两组RVP组。在以230次/分钟的频率进行5周无RVP或RVP并同时给予安慰剂或依普利酮治疗后，对犬进行电生理和超声心动图研究。评估持续性房性快速心律失常的诱发（持续时间>10分钟）、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）腔大小。接受安慰剂治疗的RVP犬出现CHF，伴有LV收缩和舒张功能障碍、左心房和LV扩大、心房ERP增加以及可诱发的持续性房性快速心律失常。RVP犬接受依普利酮治疗可显著抑制持续性房性快速心律失常的诱发，非均匀性延长心房ERP，并减轻LV舒张功能障碍，而不改变CHF时的左心房或LV扩张或射血分数。异丙肾上腺素（2 - 4微克/分钟）可逆转依普利酮在CHF中的心房抗心律失常和ERP延长作用。依普利酮对无CHF的假手术（无RVP）犬的心房ERP无影响。
依普利酮可抑制RVP诱导的CHF中持续性房性快速心律失常的诱发，选择性延长心房ERP，并减轻LV舒张期重塑。醛固酮阻断可能是预防CHF时房性快速心律失常的一种有前景的新方法。
