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: 7484284
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 47.42万
• 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/7484284
• 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（心肌梗塞的患者）和动物研究表明，食用鱼类或富含鱼油的饮食（欧米茄3多不饱和脂肪酸，N-3 PUFAS）补充剂，可显着降低心脏死亡的入口。但是，N-3 PUFAS之间关系与心律不齐风险降低的机制尚待确定。因此，我们建议使用良好的致命心室心律不齐的犬模型来研究N-3 PUFAS的安全性和功效。将在这些动物心脏中分离出的心肌细胞中检查改变心脏生理学的机制。中心假设是，使用N-3 PUFA的慢性治疗减弱了在心肌后心脏梗死的心脏突然心脏死亡模型中导致心脏猝死的电生理异常。以下具体目的将用于检验这一假设：具体目的＃1将检验以下假设：长期摄入N-3 PUFA补充剂将防止缺血引起的心律失常（通过防止重新进入和/或触发心律失常）。具体目的＃2和＃3将研究分别从狗心脏制备的心肌细胞的电生理学和钙调节的长期给药的影响。特别是，特定的目标2将检验以下假设：N-3 PUFAS将a）标准化肌膜离子电流，以改善心室肌细胞动作电位，b）在易于心室纤维化的狗中减少早期和延迟过度的落后后发生。最后，特定的目标＃3将检验以下假设：a）N-3 PUFA将阻断L型钙电流减少钙的进入，从而防止钙过载诱导的自发性钙释放，易受心室纤维化； b）N-3 PUFA将改变瑞氨烷受体功能，从而恢复易于心室纤颤的狗中更正常的肉骨质性网状钙释放； C）N-3 PUFA将改变肌质网（SR）钙负荷，从而恢复狗易于心室纤颤的狗的更正常的SR钙负荷。摘要摘要：该项目将检查心脏病发作后鱼油补充剂的安全性。该项目还将确定鱼油补充剂在心脏病发作后因致命异常心律而降低猝死的有效性。