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Mechanistic Relationships Between Ethanol and Human Atrial Fibrillation

乙醇与人类心房颤动之间的机制关系

基本信息

批准号：
8837551
负责人：
GREGORY M MARCUS
金额：
$ 58.52万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8837551
关键词：
Ablation Action Potentials Acute Address Affect Alcohol consumption Alcohols American Animal Experiments Animal Model Arrhythmia Atrial Fibrillation Atrial Premature Complexes Blood Breath Tests Cardiac Cardioscopes Cardiovascular system Case Series Cessation of life Cholesterol Chronic Clinical Conflict (Psychology)Coronary heart disease Coupled Data Development Disease Echocardiography Epidemiologic Studies Ethanol Etiology Event Evolution Experimental Models Framingham Heart Study Guidelines Health Health Care Costs Heart Heart Atrium Heart Rate Hospitalization Human Infusion procedures Intravenous Investigation Lead Left Life Maps Measurable Mechanics Methods Morbidity - disease rate Myocardium Nature Observational Study Optics Oral Patients Perception Pharmaceutical Preparations Placebos Plant Roots Post-Menopausal Hormone Replacement Therapy Predisposition Primary Prevention Procedures Process Property Recommendation Recovery Refractory Research Resources Risk Smoking Source Stroke Techniques Technology Time alcohol effect alcohol exposure binge drinking cardiovascular health chronic alcohol ingestion clinical investigation clinical practice heart rate variability heart rhythm in vivo mortality multidisciplinary novel pharmacokinetic model prevent prospective randomized trial research study sensor success time use tool

项目摘要

DESCRIPTION (provided by applicant): Ethanol is the most commonly consumed drug in the world. Atrial fibrillation (AF) is the most common arrhythmia: it currently affects several million Americans and is responsible for substantial morbidity and mortality with an estimated annual health care cost greater than 6.5 billion dollars. Small observational studies have suggested that ethanol can trigger acute episodes of AF. Large, prospective, epidemiological studies suggest that ethanol use may result in new-onset AF. However, the mechanisms underlying the potential association between either acute or chronic ethanol exposure and AF remain unknown. Investigating these causal mechanisms is important for two reasons: first, evidence of a causal association between ethanol and AF would be pertinent to the > 100 million Americans that consume ethanol. Given the common notion that ethanol is "heart healthy," demonstrating that ethanol has electrophysiological and/ or structural cardiac effects that promote AF would be particularly important. Second, understanding how an external source can acutely trigger or chronically lead to the development of AF would reveal common mechanisms underlying AF in general. There is currently no experimental model wherein human AF can be reliably triggered and no known method to prevent AF. This research could therefore open up a new field of experimental human research in AF that ultimately leads to novel therapies or clinical strategies targeting the processes responsible for AF. In Aim 1, we will perform a randomized trial of intravenous ethanol versus placebo in paroxysmal AF patients undergoing invasive ablation procedures to determine the acute electrophysiological effects of ethanol on in vivo myocardium. We will compare pre and post-infusion premature atrial contraction counts, refractory periods, conduction velocities, activation-recovery intervals, restitution properties, ad susceptibilities to induced AF. In order to assure a consistent blood ethanol concentration between patients and within-patients during the experiment, we will employ an established pharmacokinetic model to titrate and then "clamp" the ethanol infusion to maintain a steady blood ethanol concentration determined by serial breath tests. The mechanisms will be furthered elucidated in an animal model utilizing optical mapping. In order to assess the chronic effects of ethanol, Aim 2 will involve a secondary analysis of serial ethanol assessments and echocardiograms in the Framingham Heart Study to determine if ethanol-induced left atrial enlargement is responsible for incident AF. An animal model of chronic ethanol consumption will be used to further elucidate underlying mechanisms. In Aim 3, we will examine the real-time association between oral ethanol intake and AF episodes in paroxysmal AF patients wearing an automatically recording electrocardiographic monitor paired with a transdermal ethanol sensor for a four week period. The strength of the association between acute ethanol intake and AF episodes as well as the nature of the heart rhythm prior to ethanol-associated episodes (including heart rate, heart rate variability, and premature atrial contraction counts) will be determined.

描述（由申请人提供）：乙醇是世界上最常用的药物。心房颤动（AF）是最常见的心律失常：目前影响数百万人