Omega-3 Fatty Acids, Neurohumoral Activation, and Human Heart Failure

Omega-3 脂肪酸、神经体液激活和人类心力衰竭

• 批准号: 7738775
• 负责人: KEVIN D MONAHAN
• 金额: $ 19.39万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738775
• 关键词: Address; Adult; Affect; Award; Baroreflex; Biochemical; Blood Circulation; Blood Flow Velocity; Blood Pressure; Blood flow; Cardiovascular Abnormalities; Central venous pressure; Chronic; Clinical; Corn Oil; Data; Development; Diet and Nutrition; Doppler Ultrasound; Etiology; Fish Oils; Functional disorder; Future; Gender; Goals; Heart failure; Human; Ingestion; Intervention; Kidney; Limb structure; Measurement; Measures; Methods; Morbidity - disease rate; Muscle; Nerve; Nutritional; Omega-3 Fatty Acids; Outcome; Outcome Measure; Patients; Pattern; Pharmaceutical Preparations; Pharmacologic Substance; Physiological; Placebos; Play; Pressoreceptors; Prevention; Progressive Disease; Renal Blood Flow; Renin-Angiotensin-Aldosterone System; Research Design; Research Personnel; Research Project Grants; Resources; Rest; Role; Specificity; Stress; Supplementation; Sympathetic Nervous System; System; Testing; Therapeutic; Vascular resistance; Vasoconstrictor Agents; Work; age group; base; improved; innovation; insight; kidney vascular structure; mortality; novel; outcome forecast; public health relevance; response; vasoconstriction

DESCRIPTION (provided by applicant): Heart failure (HF) is a chronic and progressive disease associated with significant morbidity and mortality. As baroreflex dysfunction and neurohumoral activation contribute to the progression and poor prognosis associated with HF, therapies that favorably influence these factors are important to identify. The long-term goal of the PI is to better understand mechanisms underlying autonomic and cardiovascular abnormalities in HF. The short-term goal of the PI is to determine the effect omega-3 fatty acid supplementation exerts on baroreflex control of the circulation and neurohumoral activation in HF patients. The general working hypothesis being tested is that baroreflex dysfunction may contribute to neurohumoral activation in HF and that these factors may be favorably modified by omega-3 fatty acid supplementation. To address this topic studies with the following Specific Aims will be performed. To determine the effect of omega-3 fatty acid supplementation on: 1) muscle sympathetic nerve activity (MSNA) at rest and in response to baroreceptor loading/unloading in HF patients, 2) renal vasoconstrictor responses to baroreflex unloading in HF patients, and 3) neurohumoral activation and limb blood flow at rest and during baroreflex unloading in HF patients. Methods used to address these aims will include direct measures of efferent sympathetic nervous system outflow using peroneal microneurography, Doppler ultrasound estimates of renal blood flow velocity and whole limb blood flow, [central venous pressure], and numerous biochemical measures to assess the state of neurohumoral activation. In addition to obtaining measures at rest responses to changes in baroreceptor input (i.e., drug-induced changes in blood pressure and responses to graded central hypovolemic stress) will also be determined. These responses are important to study as baroreflex dysfunction in HF patients may underlie neurohumoral activation at rest as well as impaired modulation during application of physiological stress. Measurements obtained at study entry (baseline) will be repeated at weeks 6 and 12 of the intervention (omega-3 fatty acid supplementation) to gain insight into the temporal pattern of response. It is expected that neurohumoral activation and vascular resistance at rest will be reduced and abnormalities in baroreflex control of the circulation including modulation of neurohumoral activation will be, at least, partially restored by 12 weeks of omega-3 fatty acids supplementation in HF patients. Other groups studied will include HF patients receiving placebo (corn oil) as well as 2 groups of age-, BMI-, and gender-matched healthy adults receiving omega-3 fatty acid supplements (healthy experimental) or corn oil supplements (healthy control). Collectively, inclusion of these distinct groups will allow baseline differences attributable to HF, as well as the specificity of the responses to omega-3 fatty acids, to be determined. The findings from these novel studies will provide important insight into the therapeutic potential of omega-3 fatty acids in the management of human HF. PUBLIC HEALTH RELEVANCE: Despite significant advancements in our ability to treat heart failure with pharmacological substances this chronic and progressive disease still is associated with excessive rates of morbidity and mortality. Omega-3 fatty acids ('fish oil') may beneficially affect several important markers (neurohumoral activation and baroreflex function) associated with poor prognosis in heart failure patients. The novel studies outlined in this application will provide unique insight into the therapeutic potential of omega-3 fatty acid supplementation in the management of patients with heart failure.

描述（由申请人提供）：心力衰竭（HF）是一种慢性和进行性疾病，与明显的发病率和死亡率相关。由于压力反射功能障碍和神经肿瘤激活有助于与HF相关的进展和预后不良，因此对这些因素有利的疗法对识别很重要。 PI的长期目标是更好地理解HF自主神经和心血管异常的机制。 PI的短期目标是确定omega-3脂肪酸补充对HF患者的循环和神经肿瘤激活的压力反射控制的作用。一般的工作假设正在测试，降压反射功能障碍可能有助于HF中的神经肿瘤激活，并且这些因素可以通过补充omega-3脂肪酸来对这些因素进行有利的修饰。为了解决此主题研究，将执行以下特定目标。 To determine the effect of omega-3 fatty acid supplementation on: 1) muscle sympathetic nerve activity (MSNA) at rest and in response to baroreceptor loading/unloading in HF patients, 2) renal vasoconstrictor responses to baroreflex unloading in HF patients, and 3) neurohumoral activation and limb blood flow at rest and during baroreflex unloading in HF patients.用于解决这些目标的方法将包括使用peroneal微功能学，多普勒超声估计肾血流速度和整个肢体血流的直接衡量交感神经系统流出，[中央静脉压力]以及许多生化测量方法，以评估神经瘤活化的状态。除了获得对压力感受器输入变化的静止响应（即药物诱导的血压变化和对分级性低血容量低血容量应力的反应）外，还将确定。这些反应对于研究HF患者的压力反射功能障碍的研究很重要，在静止时可能是神经肿瘤激活的基础，并且在应用生理压力时调节受损。在研究入口时获得的测量（基线）将在干预措施的第6和第12周重复（欧米茄3脂肪酸补充），以深入了解响应的时间模式。可以预期，静止处的神经肿瘤激活和血管耐药性将降低，并且在循环系统的压力反射控制中，包括神经肿瘤活化的调节至少将在HF患者中补充omega-3脂肪酸的12周进行部分恢复。所研究的其他组将包括接受安慰剂（玉米油）的HF患者以及2组年龄，BMI和性别匹配的健康成年人接受omega-3脂肪酸补充剂（健康实验）或玉米油补充剂（健康对照）。总的来说，包含这些不同的群体将允许归因于HF的基线差异，以及旨在确定对omega-3脂肪酸的反应的特异性。这些新研究的发现将为omega-3脂肪酸在人类HF管理中的治疗潜力提供重要的见解。公共卫生相关性：尽管我们使用药理学物质治疗心力衰竭的能力取得了重大进步，但这种慢性和进行性疾病仍然与发病率和死亡率过高有关。 omega-3脂肪酸（“鱼油”）可能会影响与心力衰竭患者预后不良有关的几种重要标记（神经肿瘤激活和压力反射功能）。该应用中概述的新型研究将为omega-3脂肪酸补充在心力衰竭患者管理中的治疗潜力提供独特的见解。