Beneficial effect of eplerenone on cardiac remodelling and electrical properties of the failing heart.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
De Mello
Walmor C
WC
Department of Pharmacology, Medical Sciences Campus, School of Medicine, San Juan, PR 00936-5067, USA. wmello@rcm.upr.edu
D000818:Animals; D002469:Cell Separation; D006224:Cricetinae; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D000077545:Eplerenone; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects*
D013148:Spironolactone; D000077545:Eplerenone; D000254:Sodium-Potassium-Exchanging ATPase