ANGIOTENSIN-CONVERTING ENZYME-INHIBITION PRODUCES ELECTROPHYSIOLOGIC BUT NOT ANTIARRHYTHMIC EFFECTS IN THE INTACT HEART

Although angiotensin-converting enzyme (ACE) inhibitors are known to i nfluence favorably the structural remodeling of the heart after myocar dial infarction, the mechanisms by which ACE inhibitors improve surviv al are not well understood. The hypothesis that ACE inhibitors may pos ses antiarrhythmic activity has been studied in various isolated tissu e preparations. However, the electrophysiologic effects of ACE inhibit ors in the intact heart are not well understood, The effect of the ACE inhibitor enalaprilat on intact heart electrophysiology was studied b y using multisite optical action-potential recordings with voltage-sen sitive dyes. Action potentials were recorded simultaneously from 128 l eft ventricular epicardial sites in 15 Langendorff perfused hearts sub jected to an endocardial cryoablation procedure, which was used to res trict propagation to a thin viable rim of epicardium. Action-potential duration (APD) was significantly prolonged in 67% of preparations per fused with 5 mg/L enalaprilat. Higher concentration of enalaprilat (50 mg/L) prolonged APD in all preparations tested. This APD-prolonging e ffect persisted over a broad range of stimulus rates, indicating the a bsence of reverse use-dependent properties. Enalaprilat did not modify conduction velocity, nor did it affect spatial dispersion of repolari zation times. In addition, enalaprilat had no effect on ventricular fi brillation threshold and failed to suppress the initiation of ventricu lar tachycardia using an anatomically defined reentrant circuit. These findings indicate that in the intact heart, enalaprilat does indeed h ave electrophysiologic, effects that cause APD prolongation, particula rly at high drug concentrations. However, this effect was not of suffi cient magnitude in the guinea pig to suppress the initiation of ventri cular fibrillation or reentrant ventricular tachycardia.