Angiotensin-converting enzyme inhibition produces electrophysiologic but not antiarrhythmic effects in the intact heart.
J Cardiovasc Pharmacol
; 31(5): 734-40, 1998 May.
Article
em En
| MEDLINE
| ID: mdl-9593073
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
/
Inibidores da Enzima Conversora de Angiotensina
/
Enalapril
/
Coração
Limite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos