Effects of lisinopril on electromechanical properties and membrane currents in guinea‐pig cardiac preparations

Valenzuela, Carmen; Pérez, Onésima; Casis, Óscar; Ding, Juan; Pérez‐Vizcaíno, Francisco; Delpón, Eva; Tamargo, Juan

doi:10.1111/j.1476-5381.1993.tb13656.x

Cited by 5 publications

(1 citation statement)

References 38 publications

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“…NO and prostacyclin [110,113]. Moreover, ACEI does not modify Na + , Ca 2+ (I CaL ) or K + currents (I Kur , I Kr , I K1 ), but reduces cardiac Ca 2+ overloads by inhibiting the potentiation of I CaL produced during repetitive cardiac pacing [119].…”

Section: New Antiarrhythmic Strategiesmentioning

confidence: 99%

Pharmacological Approaches in the Treatment of Atrial Fibrillation

Tamargo¹,

Caballero²,

Delpón

2004

CMC

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial cardiovascular morbidity and mortality. The arrhythmia can be initiated and/or maintained by rapidly firing foci, single- and multiple-circuit reentry. Once initiated, AF alters atrial electrical and structural properties (atrial remodeling) in a way that promotes its own maintenance and recurrence and may alter the response to antiarrhythmic drugs. Thus, initial episodes of paroxysmal (self-terminating) AF lengthens to the point where the arrhythmia becomes persistent (requires cardioversion to restore sinus rhythm) and permanent. AF usually requires a trigger for initiation and a favorable electrophysiological and/or anatomical substrate for maintenance. The substrate includes both cardiovascular (coronary artery disease, valvular heart disease, heart failure, hypertension, dilated cardiomyopathy) and non cardiovascular diseases (thyrotoxicosis, pulmonary diseases). Accordingly, the initial step in patients with AF requires a careful assessment of symptoms and identification of underlying reversible triggers and potentially modifiable underlying structural substrate and treat them aggressively. In contrast to other cardiac arrhythmias, antiarrhythmic drugs (ADs) are the mainstay of therapy. Long-term treatment of AF is directed to restore and maintain the sinus rhythm with class I and III ADs (rhythm-control) or to allow AF to persist and ensure that the ventricular rate is controlled (rate-control) with atrioventricular nodal blocking drugs (digoxin, beta-blockers, verapamil, diltiazem) and prevent thromboembolic complications with anticoagulants. However, the long-term efficacy of ADs for preventing AF recurrence is far from ideal, because of limited efficacy (AF recurs in at least one-half of the patients) and potential side effects, particularly proarrhythmia. Thus, the choice of the appropriate AD will depend on the temporal pattern of the arrhythmia, the presence of associated diseases, easy of administration and adverse effects profile, particularly the risk of proarrhythmia. The recent finding that angiotensin converting enzyme inhibitors and beta-blockers reduce the incidence of AF in patients post myocardial infarction with left ventricular dysfunction confirmed the importance of targeting the underlying arrhythmogenic substrate. This review focuses on the mechanisms underlying AF and the mechanism of action and the efficacy and safety profile of the ADs used in the treatment of atrial fibrillation. The advantages and disadvantages of rhythm and rate control, the role pill in a pocket concept and the role of the new ADs are dicussed.

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Section: New Antiarrhythmic Strategiesmentioning

confidence: 99%

Pharmacological Approaches in the Treatment of Atrial Fibrillation

Tamargo¹,

Caballero²,

Delpón

2004

CMC

Self Cite

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Effects of lisinopril on cardiac contractility and ionic currents

Valenzuela¹,

Pérez²,

Delpón³

et al. 1994

General Pharmacology: The Vascular System

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Angiotensin-Converting Enzyme Inhibition Produces Electrophysiologic But Not Antiarrhythmic Effects in the Intact Heart

Gilat

Girouard

Pastore

et al. 1998

Journal of Cardiovascular Pharmacology

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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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Effects of lisinopril on electromechanical properties and membrane currents in guinea‐pig cardiac preparations

Cited by 5 publications

References 38 publications

Pharmacological Approaches in the Treatment of Atrial Fibrillation

Pharmacological Approaches in the Treatment of Atrial Fibrillation

Effects of lisinopril on cardiac contractility and ionic currents

Angiotensin-Converting Enzyme Inhibition Produces Electrophysiologic But Not Antiarrhythmic Effects in the Intact Heart

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