厄贝沙坦对心力衰竭大鼠心室电生理重构及瞬时外向钾电流的影响

目的探讨厄贝沙坦对心力衰竭大鼠心室肌细胞电生理重构及瞬时外向钾电流(Ito)的影响。方法采用腹主动脉缩窄法建立心力衰竭大鼠模型,将制模成功的21只大鼠随机分为心力衰竭治疗组(治疗组,10只)、心力衰竭对照组(对照组,11只)和另选10只大鼠为假手术组。术后16周测定3组大鼠心率、QRS时间、QT间期、校正QT间期、心室有效不应期以及心功能。采用酶解法获得单个大鼠心室肌细胞并以标准全细胞膜片钳技术记录Ito。结果与假手术组比较,对照组和治疗组大鼠血压、左心室舒张末压明显升高,对照组大鼠校正QT间期、心室有效不应期明显延长,心室肌细胞Ito密度明显减少;治疗组大鼠心室肌细胞Ito密度较对照组明显增加,差异有统计学意义(P0.05,P0.01)。与对照组比较,治疗组大鼠心室有效不应期明显缩短(P0.05)。结论厄贝沙坦治疗能明显改善慢性心力衰竭大鼠电生理失稳态变化,可能与其增加心室肌细胞膜Ito有关。

Effect of irbesartan on electrophysiological remodeling and transient outward potassium current in failing hearts of rats

Objective To determine the effects of irbesartan on cardiac electrophysiological remodeling and transient outward potassium current(Ito) in isolated ventricular myocytes of rats with heart failure.Methods A heart failure model was established by surgical abdominal aortic stenosis in adult SD rats.Eight weeks later,the rats with heart failure were divided randomly into the group treated with irbesartan [CHF-T group,20 mg/(kg·d)] and group receiving placebo(CHF-C group).Sham-operated group served as negative controls(PS group).Blood pressure and left ventricular end-diastolic pressure were recorded. Cardiac electrophysiological parameters including ventricular effective refractory period were measured.Single ventricular myocytes of rats were isolated by enzymatic dissociation.The whole-cell patch-clamp recording technique was used to record Ito.Results Compared with PS group,heart rate, QT-interval and ventricular effective refractory period of rats in CHF-C group and CHF-T group increased. Heart rate,and ventricular effective refractory period of rats in CHF-T group decreased compared with CHF-C group (P<0.05,P< 0.01).The current density of Ito in CHF-T group was larger significantly than that in CHF-C group (P < 0.05).Compared with CHF-C group and PS group,the current density of Ito in myocytes of left ventricles in CHF-T group upregulated significantly.Conclusion Irbesartan is effective in preventing cardiac electrophysiological instability in rats with heart failure and this may be related to increasing Ito of ventricular myocytes.