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: 7872853
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 49.3万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872853
• 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; Data; Defibrillators; Developed 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; Oleic Acids; Omega-3 Fatty Acids; Patients; Pharmaceutical Preparations; Phase; Phospholipids; Physiology; Placebos; Plant Leaves; Polyunsaturated Fatty Acids; Population; Randomized; Regulation; Reporting; Research Personnel; Resistance; Risk; Ryanodine; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Safety; Schedule; Secondary Prevention; Sudden Death; Tachyarrhythmias; Testing; United States; Vent; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Ventricular Tachycardia; active method; base; capsule; healing; heart rhythm; high risk; improved; in vivo; mortality; novel strategies; patient population; prevent; programs; receptor function; safety testing; 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(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，食用鱼类或补充鱼油(omega-3多不饱和脂肪酸，n-3多不饱和脂肪酸)可显著降低心源性猝死的发生率。然而，n-3多不饱和脂肪酸与降低心律失常风险之间的关系的潜在机制仍有待确定。因此，我们建议使用已建立的犬致死性室性心律失常模型来研究n-3多不饱和脂肪酸的安全性和有效性。改变心脏电生理学的机制将在从这些动物的心脏分离的心肌细胞中进行检测。中心假设是，在心肌梗塞后心源性猝死的犬模型中，n-3PUFAs的慢性治疗可以减轻导致心源性猝死的电生理异常。以下特定目标将用于验证这一假设：特定目标#1将测试长期摄入n-3多不饱和脂肪酸补充剂将防止缺血引起的快速性心律失常(通过防止折返性和/或触发的心律失常)的假设。具体目标#2和#3将分别研究长期服用n-3PUFAs对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，《特定目标2》将检验以下假设：N-3多不饱和脂肪酸将a)使改善心室肌细胞动作电位的肌膜离子电流正常化，b)减少易发生室颤的犬的早期和延迟后除极。最后，特定目标#3将检验以下假设：a)n-3多不饱和脂肪酸可阻断L型钙电流，减少钙离子内流，从而防止钙超载引起的室颤易感犬自发钙释放；b)n-3多不饱和脂肪酸可改变兰尼定受体功能，使室颤易感犬恢复更正常的肌浆网钙释放；以及c)n-3多不饱和脂肪酸可改变肌浆网(SR)钙负荷，使室颤易感犬恢复更正常的SR钙负荷。文章摘要：这个项目将研究心脏病发作后服用鱼油补充剂的安全性。该项目还将确定鱼油补充剂在减少因心脏病发作后致命的异常心律而导致的猝死方面的有效性。

项目成果

Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model.

• DOI: 10.3389/fphys.2016.00225
• 发表时间: 2016
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Bonilla IM;Nishijima Y;Vargas-Pinto P;Baine SH;Sridhar A;Li C;Billman GE;Carnes CA
• 通讯作者: Carnes CA

Effect of dietary omega-3 polyunsaturated Fatty acids on heart rate and heart rate variability in animals susceptible or resistant to ventricular fibrillation.

• DOI: 10.3389/fphys.2012.00071
• 发表时间: 2012
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Billman GE

Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

• DOI: 10.1161/circep.111.966739
• 发表时间: 2012-06-01
• 期刊: Circulation. Arrhythmia and electrophysiology
• 作者: Billman GE;Carnes CA;Adamson PB;Vanoli E;Schwartz PJ
• 通讯作者: Schwartz PJ

Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness.

• DOI: 10.1161/circep.113.000404
• 发表时间: 2013-10
• 期刊: Circulation. Arrhythmia and electrophysiology
• 作者: Glukhov AV;Hage LT;Hansen BJ;Pedraza-Toscano A;Vargas-Pinto P;Hamlin RL;Weiss R;Carnes CA;Billman GE;Fedorov VV
• 通讯作者: Fedorov VV

Effect of twitch interval duration on the contractile function of subsequent twitches in isolated rat, rabbit, and dog myocardium under physiological conditions.

• DOI: 10.1152/japplphysiol.01170.2010
• 发表时间: 2011-07
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: Ying Xu;M. Monasky;Nitisha Hiranandani;K. M. Haizlip;G. Billman;P. Janssen