Angiotensin-converting enzyme inhibition produces electrophysiologic but not antiarrhythmic effects in the intact heart.
Although angiotensin-converting enzyme (ACE) inhibitors are known to influence favorably the structural remodeling of the heart after myocardial infarction, the mechanisms by which ACE inhibitors improve survival are not well understood. The hypothesis that ACE inhibitors may possess antiarrhythmic activity has been studied in various isolated tissue preparations. However, the electrophysiologic effects of ACE inhibitors in the intact heart are not well understood. The effect of the ACE inhibitor enalaprilat on intact heart electrophysiology was studied by using multisite optical action-potential recordings with voltage-sensitive dyes. Action potentials were recorded simultaneously from 128 left ventricular epicardial sites in 15 Langendorff perfused hearts subjected to an endocardial cryoablation procedure, which was used to restrict propagation to a thin viable rim of epicardium. Action-potential duration (APD) was significantly prolonged in 67% of preparations perfused with 5 mg/L enalaprilat. Higher concentration of enalaprilat (50 mg/L) prolonged APD in all preparations tested. This APD-prolonging effect persisted over a broad range of stimulus rates, indicating the absence of reverse use-dependent properties. Enalaprilat did not modify conduction velocity, nor did it affect spatial dispersion of repolarization times. In addition, enalaprilat had no effect on ventricular fibrillation threshold and failed to suppress the initiation of ventricular tachycardia using an anatomically defined reentrant circuit. These findings indicate that in the intact heart, enalaprilat does indeed have electrophysiologic effects that cause APD prolongation, particularly at high drug concentrations. However, this effect was not of sufficient magnitude in the guinea pig to suppress the initiation of ventricular fibrillation or reentrant ventricular tachycardia.
Gilat
E
E
The Department of Medicine, The Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, and The Veterans Affairs Medical Center, Cleveland, Ohio 44106-7207, USA.
Girouard
S D
SD
Pastore
J M
JM
Laurita
K R
KR
Rosenbaum
D S
DS
D000200:Action Potentials / Q000187:drug effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D004594:Electrophysiology; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril