Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstraße 6, Erlangen, Germany.
Basic Res Cardiol. 2012 Sep;107(5):290. doi: 10.1007/s00395-012-0290-4. Epub 2012 Aug 2.
Pressure overload is associated with cardiac hypertrophy and electrical remodeling. Here, we investigate the effects of the antioxidant N-acetylcysteine (NAC) on the cellular cardiac electrophysiology of female Sprague-Dawley rats with ascending aortic stenosis (AS). Rats were treated with NAC (1 g/kg body weight) or control solution 1 week before the intervention and in the week following AS or sham operation. Seven days after the operation, blood pressure and left ventricular pressure were measured before the heart was excised. Single cells were isolated from epicardial and endocardial layers of the left ventricular free wall and investigated using the whole-cell patch-clamp technique. Systolic blood pressure and left ventricular peak pressure were not significantly altered in the NAC group. NAC reduced the increase (p < 0.001) in the relative left ventricular weight (p < 0.05) as well as the increase (p < 0.001) in cell capacitance in epicardial (p < 0.05), but not in endocardial myocytes of AS animals. The L-type Ca(2+) current (I (CaL)) was significantly increased by AS in epicardial (+19 % at 0 mV, p < 0.01) but not in endocardial myocytes. NAC completely prevented this increase in I (CaL) (p < 0.01). The current density of the transient outward K(+) current (I (to)) was not affected by AS or NAC. Action potential duration to 90 % repolarization was significantly prolonged in epicardial (p < 0.01) as well as in endocardial (p < 0.001) cells of AS animals. NAC prevented the AP prolongation in epicardial myocytes only (p < 0.05). We conclude that reducing oxidative stress in pressure overload can prevent electrical remodeling and ameliorate hypertrophy in epicardial but not in endocardial myocytes.
压力超负荷与心肌肥厚和电重构有关。在这里，我们研究了抗氧化剂 N-乙酰半胱氨酸 (NAC) 对升主动脉狭窄 (AS) 雌性 Sprague-Dawley 大鼠心脏细胞电生理学的影响。大鼠在干预前 1 周和 AS 或假手术后的 1 周内用 NAC（1 g/kg 体重）或对照溶液治疗。手术后 7 天，在取出心脏之前测量血压和左心室压力。从左心室游离壁心外膜和心内膜层分离出单细胞，并使用全细胞膜片钳技术进行研究。NAC 组的收缩压和左心室峰值压力没有明显改变。NAC 降低了左心室相对重量的增加（p < 0.001）（p < 0.05）以及心外膜细胞（p < 0.05）但不是 AS 动物的心内膜细胞电容的增加。L 型 Ca(2+)电流（I (CaL)）在 AS 中在心外膜中显著增加（0 mV 时增加 19%，p < 0.01），但在心内膜细胞中没有增加。NAC 完全阻止了 I (CaL) 的这种增加（p < 0.01）。瞬时外向 K(+)电流（I (to)）的电流密度不受 AS 或 NAC 的影响。AP 复极至 90%时，心外膜（p < 0.01）和心内膜（p < 0.001）细胞的动作电位时程明显延长。NAC 仅在心外膜细胞中防止 AP 延长（p < 0.05）。我们得出结论，减少压力超负荷中的氧化应激可以预防电重构并改善心外膜但不是心内膜心肌细胞的肥大。
