De Mello Walmor C
Department of Pharmacology, Medical Sciences Campus, School of Medicine, San Juan, PR 00936-5067, USA.
J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):40-6. doi: 10.3317/jraas.2006.005.
The effect of chronic administration of eplerenone on cardiac remodelling and electrical properties was investigated in the failing heart of cardiomyopathic hamsters (TO-2) at five months of age.
Two-month-old hamsters were treated with eplerenone (200 mg/kg/day) administered into the chow for a period of three months. Measurements of membrane potential were performed with intracellular microelectrodes connected to a high impedance DC amplifier. The thickness of the ventricular wall as well as the area of fibrosis were measured. To investigate the influence of eplerenone on the electrogenic sodium pump myocytes were isolated from the ventricle and the pump current density was measured in voltage clamped cells using the whole cell clamp configuration.
The results indicated that: 1) the width of the left and right ventricular wall was significantly reduced; 2) the heart weight/body weight ratio was decreased by 38+/-2.4% (n=24) (p<0.05); 3) the fibrotic area in the left ventricle (LV) was reduced by 12.6+/-2% (n=25) (p<0.05); 4) the incidence of cardiac arrhythmias was decreased from 58+/-3.8% (n=20) in the control to 40+/-4.1% (n=20) (p<0.05) in animals treated with eplerenone. Moreover, a significant reduction in the dispersion of the QT interval was found with the drug; 5) eplerenone increased the resting potential of ventricular fibres from 64.3+/-1.5 mV to 73.4+/-1.4 mV (n=30) (p<0.05), an effect related to the activation of an electrogenic sodium pump. The conduction velocity, in longitudinal direction, was enhanced from 50+/-2.2 cm/s (n=10) in the controls to 59+/-2.4 cm/s (n=13) (p<0.05) in animals treated with eplerenone.
Eplerenone reduces cardiac remodelling, the incidence of cardiac arrhythmias and improves impulse propagation, an effect in part related to the antifibrotic effect of the drug but also to the activation of the electrogenic sodium pump.
研究了依普利酮长期给药对5月龄心肌病仓鼠（TO - 2）衰竭心脏的心脏重塑和电特性的影响。
对2月龄仓鼠进行为期3个月的依普利酮（200mg/kg/天）灌胃治疗。使用连接到高阻抗直流放大器的细胞内微电极测量膜电位。测量心室壁厚度和纤维化面积。为研究依普利酮对生电性钠泵的影响，从心室分离出心肌细胞，采用全细胞钳制模式在电压钳制的细胞中测量泵电流密度。
结果表明：1）左、右心室壁宽度显著减小；2）心脏重量/体重比降低了38±2.4%（n = 24）（p < 0.05）；3）左心室纤维化面积减少了12.6±2%（n = 25）（p < 0.05）；4）心律失常发生率从对照组的58±3.8%（n = 20）降至依普利酮治疗组的40±4.1%（n = 20）（p < 0.05）。此外，发现该药物可显著降低QT间期离散度；5）依普利酮使心室纤维静息电位从64.3±1.5mV增加到73.4±1.4mV（n = 30）（p < 0.05），这一作用与生电性钠泵的激活有关。在纵向方向上，传导速度从对照组的50±2.2cm/s（n = 10）提高到依普利酮治疗组的59±2.4cm/s（n = 13）（p < 0.05）。
依普利酮可减轻心脏重塑、降低心律失常发生率并改善冲动传导，这一作用部分与该药物的抗纤维化作用有关，也与生电性钠泵的激活有关。
