Stambler Bruce S, Laurita Kenneth R, Shroff Sunil C, Hoeker Gregory, Martovitz Nichole L
University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
Heart Rhythm. 2009 Jun;6(6):776-83. doi: 10.1016/j.hrthm.2009.02.005. Epub 2009 Feb 12.
Aldosterone blockade reduces sudden cardiac death in heart failure, but the underlying mechanism is unclear.
This study's aim was to determine whether chronic eplerenone treatment protects against detrimental ventricular electrical remodeling and development of an arrhythmogenic substrate in a rapid ventricular pacing (RVP)-induced heart failure model.
Dogs were assigned randomly to oral placebo or eplerenone treatment and divided into 4 groups: 2 sham-operated (no RVP) and 2 RVP groups. After 5 weeks of no RVP or RVP along with concurrent placebo or eplerenone treatment, dogs underwent echocardiographic assessments of systolic function and chamber size and electrophysiologic measurements of ventricular repolarization, refractoriness, conduction, tachyarrhythmia inducibility, and myocardial activation delays after premature stimulation.
Eplerenone failed to prevent left ventricular systolic dysfunction or chamber enlargement in RVP dogs. Eplerenone attenuated prolongation of ventricular repolarization and refractoriness, increases in dispersion of repolarization and refractoriness, fractionation of ventricular electrograms, and delays in myocardial activation after premature stimulation at short coupling intervals and improved arrhythmia vulnerability score in RVP dogs with heart failure. Ventricular tachyarrhythmia inducibility in heart failure dogs was predicted by activation delays after premature stimulation at short coupling intervals, which were prevented by eplerenone. Eplerenone did not alter electrophysiological parameters in no-RVP dogs without heart failure.
Eplerenone attenuates heart failure-related ventricular electrical remodeling and tachyarrhythmia vulnerability. Inhibition of myocardial activation delays during premature excitation may contribute to preventing development of an arrhythmogenic ventricular substrate in heart failure.
醛固酮拮抗剂可降低心力衰竭患者的心源性猝死，但潜在机制尚不清楚。
本研究旨在确定在快速心室起搏（RVP）诱导的心力衰竭模型中，慢性依普利酮治疗是否能预防有害的心室电重构和致心律失常基质的形成。
将犬随机分为口服安慰剂或依普利酮治疗组，再分为4组：2组假手术组（无RVP）和2组RVP组。在无RVP或RVP同时给予安慰剂或依普利酮治疗5周后，对犬进行收缩功能和心室大小的超声心动图评估，以及心室复极化、不应期、传导、室性快速心律失常诱发率和早搏刺激后心肌激活延迟的电生理测量。
依普利酮未能预防RVP犬的左心室收缩功能障碍或心室扩大。依普利酮可减轻RVP心力衰竭犬在短联律间期时的心室复极化和不应期延长、复极化和不应期离散度增加、心室电图碎裂以及早搏刺激后心肌激活延迟，并改善心律失常易感性评分。心力衰竭犬的室性快速心律失常诱发率可通过短联律间期早搏刺激后的激活延迟来预测，而依普利酮可预防这种延迟。依普利酮对无心力衰竭的无RVP犬的电生理参数无影响。
依普利酮可减轻心力衰竭相关的心室电重构和室性快速心律失常易感性。抑制早搏兴奋时的心肌激活延迟可能有助于预防心力衰竭中致心律失常心室基质的形成。
