Dietary Omega-3 Fatty Acids and Sudden Cardiac Death

膳食 Omega-3 脂肪酸与心源性猝死

• 批准号: 7317380
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 46.98万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7317380
• 关键词: Action Potentials; Acute; Adverse effects; Animal Model; Animals; Anti-Arrhythmia Agents; Arrhythmia; Attenuated; Calcium; Calcium Signaling; Calories; Canis familiaris; Cardiac; Cardiac Myocytes; Cardiovascular system; Cause of Death; Cessation of life; Chronic; Clinical Trials; Collection; Conflict (Psychology); Consultations; Consumption; Control Groups; Corn Oil; Count; Data; Defibrillators; Developed Countries; Developing Countries; Development; Diet; Dose; Effectiveness; Electric Stimulation; Electrophysiology (science); Epidemiologic Studies; Event; Exhibits; Fatty Acids; Fatty acid glycerol esters; Fish Oils; Fishes; Frequencies; Healed; Heart; Heart Arrest; Hospitals; Implant; In Vitro; Incidence; Infarction; Ingestion; Investigation; Ions; Ischemia; Left; Life; Malignant - descriptor; Mediating; Modeling; Monounsaturated Fatty Acids; Muscle Cells; Myocardial Infarction; Myocardial Ischemia; Numbers; Oleic Acid; Oleic Acids; Omega-3 Fatty Acids; Patients; Pharmaceutical Preparations; Phase; Phospholipids; Physiology; Placebos; Plant Leaves; Polyunsaturated Fatty Acids; Population; Randomized; Range; Rate; Regulation; Reporting; Research Personnel; Resistance; Risk; Ryanodine; Ryanodine Receptor Calcium Release Channel; Safety; Schedule; Secondary Prevention; Standards of Weights and Measures; Sudden Death; Tachyarrhythmias; Testing; United States; United States Environmental Protection Agency; Vent; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Ventricular Tachycardia; base; capsule; day; healing; heart rhythm; improved; in vivo; mortality; novel strategies; prevent; programs; receptor function; sudden cardiac death; treatment duration

DESCRIPTION (provided by applicant): Epidemiological studies, clinical trials (patients with myocardial infarction), and animal studies have demonstrated that fish consumption, or diets enriched with fish oil (omega-3 polyunsaturated fatty acids, n-3 PUFAs) supplements, significantly reduced the incidence of sudden cardiac death. However, the mechanisms underlying the relationship between n-3 PUFAs and a reduced risk for cardiac arrhythmias remain to be determined. Therefore, we propose to investigate the safety and efficacy of n-3 PUFAs using a well-established canine model of lethal ventricular arrhythmias. The mechanisms altering cardiac electrophysiology will be examined in cardiac myocytes isolated from the hearts of these animals. The central hypothesis is that chronic treatment with n-3 PUFAs attenuates the electrophysiological abnormalities contributing to sudden cardiac death in a post-myocardial infarction canine model of sudden cardiac death. The following specific aims will be used to test this hypothesis: Specific Aim #1 will test the hypothesis that the chronic ingestion of n-3 PUFA supplements will prevent ischemia-induced tachyarrhythmias (by preventing re-entrant and/or triggered arrhythmias). Specific Aims #2 and #3 will investigate the effects of the chronic administration of n-3 PUFAs on the electrophysiology and calcium regulation of cardiomyocytes prepared from the hearts of the dogs, respectively. In particular, Specific Aim 2 will test the following hypotheses: n-3 PUFAs will a) normalize the sarcolemmal ion currents improving the ventricular myocyte action potential and b) reduce both early and delayed afterdepolarizations in dogs susceptible to ventricular fibrillation. Finally, Specific Aim #3 will test the following hypotheses: a) n-3 PUFAs will block L-type calcium current reducing calcium entry and thereby preventing calcium overload-induced spontaneous calcium release in dogs susceptible to ventricular fibrillation; b) n-3 PUFAs will alter ryanodine receptor function, restoring a more normal sarcoplasmic reticular calcium release in dogs susceptible to ventricular fibrillation; and c) n-3 PUFAs will alter the sarcoplasmic reticular (SR) calcium load, restoring a more normal SR calcium load in the dogs susceptible to ventricular fibrillation. Lay summary: This project will examine the safety of fish oil supplements after a heart attack. This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack.

描述（由申请人提供）：流行病学研究、临床试验（心肌梗塞患者）和动物研究表明，食用鱼类或富含鱼油（omega-3 多不饱和脂肪酸，n-3 PUFA）补充剂的饮食可显着降低心源性猝死的发生率。然而，n-3 PUFA 与降低心律失常风险之间关系的机制仍有待确定。因此，我们建议使用完善的犬致死性室性心律失常模型来研究 n-3 PUFA 的安全性和有效性。将在从这些动物心脏分离的心肌细胞中检查改变心脏电生理学的机制。核心假设是，在心肌梗塞后的犬心源性猝死模型中，n-3 PUFA 的长期治疗可减轻导致心源性猝死的电生理学异常。以下具体目标将用于检验这一假设： 具体目标 #1 将检验以下假设：长期摄入 n-3 PUFA 补充剂将预防缺血引起的快速心律失常（通过预防折返性和/或触发性心律失常）。具体目标 #2 和 #3 将分别研究长期施用 n-3 PUFA 对从狗心脏制备的心肌细胞的电生理学和钙调节的影响。特别是，具体目标 2 将测试以下假设：n-3 PUFA 将 a) 使肌膜离子电流正常化，改善心室肌细胞动作电位，b) 减少易患心室颤动的狗的早期和延迟后除极。最后，具体目标#3 将测试以下假设： a) n-3 PUFA 将阻断 L 型钙电流，减少钙进入，从而防止易患心室颤动的狗中钙超载引起的自发钙释放； b) n-3 PUFA 将改变兰尼碱受体功能，使易患心室颤动的狗恢复更正常的肌浆网状钙释放； c) n-3 PUFA 将改变肌浆网状 (SR) 钙负荷，使易患心室颤动的狗恢复更正常的 SR 钙负荷。概要：该项目将检查心脏病发作后补充鱼油的安全性。该项目还将确定鱼油补充剂在减少心脏病发作后因致命性心律失常导致的猝死方面的有效性。