Hao Zhang1, Hongmei Ruan1, Dolkun Rahmutula1, Emily Wilson1, Gregory M Marcus2, Vasanth Vedantham3, Jeffrey E Olgin4. 1. Division of Cardiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California. 2. Division of Cardiology, Electrophysiology Section, University of California San Francisco, San Francisco, California. 3. Division of Cardiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California; Division of Cardiology, Electrophysiology Section, University of California San Francisco, San Francisco, California. 4. Division of Cardiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California; Division of Cardiology, Electrophysiology Section, University of California San Francisco, San Francisco, California; Cardiac Electrophysiology and Cardiovascular Research Institute, University of California San Francisco, San Francisco, California. Electronic address: jeffrey.olgin@ucsf.edu.
Abstract
BACKGROUND: Even though ethanol consumption has been associated with risk of atrial fibrillation (AF), little is known about how ethanol affects atrial electrophysiology. OBJECTIVE: The purpose of this study was to study the electrophysiological effect of ethanol on rat AF. METHODS: Atrial optical mapping was performed on male Long Evans rat hearts with escalating concentrations of ethanol (0, 1, 2, and 3 mM). In addition, patch-clamp recordings on isolated atrial myocytes were performed. In chronic ethanol study, rats were divided into control and chronic ethanol groups (20% ethanol in drinking water for 6 months). Atrial optical mapping, histology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were performed in chronic rats. RESULTS: Acute ethanol perfusion increased AF vulnerability (0% at 0 mM, 0% at 1 mM, 57.1% at 2 mM, and 100% at 3 mM) in a dose-related response. Ethanol infusion decreased conduction velocities (CVs) in both atria and shortened effective refractory periods (ERP) only in the right atria with increased in dispersion of refractoriness. Action potential duration at 50% and 90% repolarization from right atrial myocytes were shortened, with corresponding increase of sustained potassium current. Chronic ethanol consumption increased AF inducibility (10% control vs 95.2% chronic ethanol). CVs in both atria were significantly decreased. ERP of the right atrium was shortened, and dispersion of ERP was increased. Expression (mRNA) of KCNQ1 and connexin40 were increased, but KCNA5 was decreased in the right atrium of rats exposed to chronic ethanol. CONCLUSION: Acute and chronic exposure to ethanol increases AF vulnerability by slowing CV, shortening right atrial ERP, and increasing dispersion of ERP.
BACKGROUND: Even though ethanol consumption has been associated with risk of atrial fibrillation (AF), little is known about how ethanol affects atrial electrophysiology. OBJECTIVE: The purpose of this study was to study the electrophysiological effect of ethanol on ratAF. METHODS: Atrial optical mapping was performed on male Long Evans rat hearts with escalating concentrations of ethanol (0, 1, 2, and 3 mM). In addition, patch-clamp recordings on isolated atrial myocytes were performed. In chronic ethanol study, rats were divided into control and chronic ethanol groups (20% ethanol in drinking water for 6 months). Atrial optical mapping, histology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were performed in chronic rats. RESULTS: Acute ethanol perfusion increased AF vulnerability (0% at 0 mM, 0% at 1 mM, 57.1% at 2 mM, and 100% at 3 mM) in a dose-related response. Ethanol infusion decreased conduction velocities (CVs) in both atria and shortened effective refractory periods (ERP) only in the right atria with increased in dispersion of refractoriness. Action potential duration at 50% and 90% repolarization from right atrial myocytes were shortened, with corresponding increase of sustained potassium current. Chronic ethanol consumption increased AF inducibility (10% control vs 95.2% chronic ethanol). CVs in both atria were significantly decreased. ERP of the right atrium was shortened, and dispersion of ERP was increased. Expression (mRNA) of KCNQ1 and connexin40 were increased, but KCNA5 was decreased in the right atrium of rats exposed to chronic ethanol. CONCLUSION: Acute and chronic exposure to ethanol increases AF vulnerability by slowing CV, shortening right atrial ERP, and increasing dispersion of ERP.
Authors: Gregory M Marcus; Jonathan W Dukes; Eric Vittinghoff; Gregory Nah; Nitish Badhwar; Joshua D Moss; Randall J Lee; Byron K Lee; Zian H Tseng; Tomos E Walters; Vasanth Vedantham; Rachel Gladstone; Shannon Fan; Emily Lee; Christina Fang; Kelsey Ogomori; Trisha Hue; Jeffrey E Olgin; Melvin M Scheinman; Henry Hsia; Vijay A Ramchandani; Edward P Gerstenfeld Journal: JACC Clin Electrophysiol Date: 2021-01-27