A PUFA Dietary Intervention for Heart Rate

PUFA 饮食干预心率

• 批准号: 7963888
• 负责人: Edward Lakatta
• 金额: $ 41.56万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7963888
• 关键词: Acids; Affect; Age; Calcium; Cardiac; Cardiovascular system; Cells; Cessation of life; Chemistry; Clinical; Data Analyses; Diet; Dietary Intervention; Disease; Elderly; Epidemiologic Studies; Epidemiology; Event; Fatty Acids; Fishes; Heart Atrium; Heart Rate; Homeostasis; Image; Individual; Industry; Ion Channel; Ions; Link; Membrane; Membrane Lipids; Membrane Microdomains; Methodology; Modeling; Nerve; Nodal; Omega-3 Fatty Acids; Oryctolagus cuniculus; Outcome; Outcome Study; Oxidation-Reduction; Pacemakers; Pharmaceutical Preparations; Property; Proteins; Protocols documentation; Rattus; Residual state; Rest; Rodent; Sarcoplasmic Reticulum; Signaling Molecule; Signaling Protein; Skin; Surface; Tissues; Upper arm; Ventricular; Ventricular Fibrillation; novel; patch clamp

We, and others, have demonstrated dietary content of long chain polyunsaturated fattly acids (PUFA) affects their incorporation into cell membrane lipid rafts. PUFA have a dramatic impact on cell ion homeostasis and redox chemistry. Omega 3 PUFA, the good variety of PUFAs, type typified by Docosohexanoic acid, protect from lethal post-ischemic arrythmias, whilst the Omega 6, bad variety of PUFA, promote theses arrythmias. With advancing age in rodents, membrane Omega 3 decrease and Omega 6 increase. Old rats are extremely vulnerable to post ischemic ventricular fibrillation. The age-associated change in membrane PUFA profile is completely reversed by diets rich in Omega 3 PUFA, as is the vulnerability to ventricular fibrillation. Accumulating epidemiological evidence indicates that dietary PUFA (from fish) confer secondary protection from death due to cardiovascular events related to Alzheimers CV disease. In these studies, it was noted that those individuals who consumed diets high in Omega 3 PUFA also had a reduction in resting heart rate. Numerous other recent epidemiological studies have demonstrated a beneficial effect to a lower (but normal) heart rate with respect to morbid outcomes with CV disease. The Pharma industry has begun to capitalize upon these discoveries by initiating clinical outcome studies to reduce heart rate using bradycardic drug as the active arm. Results to date demonstrate that there is a moderate, but significant reduction in baseline and intrinsic (elimination of sympathetic and residual nerve control) heart rate following 40-60 day diet of Omega 3 PUFA compared to a diet of Omega 6 PUFA. Analysis of data is ongoing for studies employed to identify mechanistic causes for altered beating rates in isolated sinoatrial nodal cells between the two dietary groups: 1) patch clamp protocols to evaluate their beating rate and also possible changes in some other electrophysiological parameters, 2) skinned cell methodologies to compare local calcium release (LCR) and sarcoplasmic reticulum (SR) load, and 3) cytosolic Ca2+ transients. The large amount of cardiac tissue collected is being analyzed for fatty acid content and incorporation.

我们和其他人表现出长链多不饱和酸性酸（PUFA）的饮食含量影响其掺入细胞膜脂质筏中。 PUFA对细胞离子稳态和氧化还原化学的影响产生巨大影响。 Omega 3 Pufa，种类繁多的PUFA，以Docosohexanoic酸为代表的类型，可免受致命后缺血后的arrythmias的保护，而Omega 6（不良的PUFA）促进了Theses Arrythmias。 随着啮齿动物年龄的增长，膜欧米茄3减少，欧米茄6增加。 老鼠极易容易出现缺血性心室纤颤。 富含Omega 3 PUFA的饮食，膜PUFA谱的年龄相关的变化以及对心室纤颤的脆弱性也完全逆转。 累积的流行病学证据表明，饮食中的PUFA（来自鱼类）赋予与阿尔茨海默氏症CV病有关的心血管事件引起的次要保护，以免死亡。 在这些研究中，有人指出，那些在Omega 3 Pufa中食用饮食习惯的人的静息心率也降低了。关于CV疾病的病态结果，许多其他最近的流行病学研究表明，对较低（但正常）的心率具有有益作用。 制药行业已开始通过启动临床结果研究来利用这些发现，以减少心跳药作为活跃部门的心率。 迄今为止的结果表明，与Omega 6 PUFA的饮食相比，在40-60天饮食之后，基线和内在（消除交感神经控制和残留神经控制）的心率显着降低（消除交感神经和残留神经控制）。 为了确定两个饮食组之间孤立的弦乐节点细胞中的殴打率改变的机械原因的研究的数据分析正在进行中：1）斑块夹夹协议，以评估其跳动率，并在其他一些电生理学参数中可能发生变化，2）皮肤细胞方法，以比较局部钙化局部和sarcopopoplamic capoplamic capoplamic capoplimic capoplimic capoplimic capocumic capoplimic sr sr sr sr sr，瞬态。 正在分析收集的大量心脏组织中的脂肪酸含量和掺入。