Antiarrhythmic Effects of Losartan and Enalapril in Canine Pulmonary Vein Sleeve Preparations

• Published in: Journal of cardiovascular electrophysiology Vol. 22; no. 6; pp. 698 - 705
• Main Authors: Sicouri, Serge, Cordeiro, JONATHAN M., Talarico, Michael, Antzelevitch, Charles
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.06.2011
• Subjects: angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; Animals; Anti-Arrhythmia Agents - administration & dosage; antiarrhythmic drugs; atrial fibrillation; Dogs; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril - administration & dosage; Heart Conduction System - drug effects; Heart Conduction System - physiopathology; Heart Rate - drug effects; Losartan - administration & dosage; Pulmonary Veins - drug effects; Pulmonary Veins - physiopathology; sodium channel blocker
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.2010.01972.x

Antiarrhythmic Effect of Losartan and Enalapril. Introduction: Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II‐receptor blockers (ARBs) are prototypes of “upstream” therapy for the management of atrial fibrillation (AF). Ectopic activity arising from the PV sleeves plays a prominent role in the development of AF. Methods: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (ACh, 1 μM), isoproterenol (1 μM), high calcium ([Ca2+]o= 5.4 mM) or a combination was used to induce early or delayed afterdepolarizations (EADs or DADs) and triggered activity. Results: The ARB losartan (1 μM, n = 5) and the ACE inhibitor enalapril (10 μM, n = 5) produced no significant change in action potential duration, maximum rate of rise of action potential upstroke (Vmax), action potential amplitude or take‐off potential at basic cycle lengths of 200 to 2000 ms. Losartan (1 μM) and enalapril (10–20 μM) markedly attenuated or suppressed EADs and DAD‐induced triggered activity elicited by exposure of the PV sleeves to ACh, isoproterenol or high calcium following rapid pacing in 6 of 6 (losartan) and 4 of 5 (enalapril) PV sleeve preparations. Neither losartan nor enalapril altered Ca2+ or K+ channel currents in enzymatically‐dissociated atrial myocytes at these concentrations. Conclusions: Our data suggest that in addition to their “upstream” effects to reduce atrial structural remodeling, ACE inhibitors and ARBs exert a “direct” antiarrhythmic effect by suppressing triggers responsible for the genesis of AF and other atrial arrhythmias. (J Cardiovasc Electrophysiol, Vol. 22, pp. 698‐705, June 2011)