Pulmonary Limitations in Chronic Heart Failure

慢性心力衰竭的肺部局限性

• 批准号: 7820942
• 负责人: BRUCE D JOHNSON
• 金额: $ 1.59万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7820942
• 关键词: Address; Affect; Age; Alleles; Angiotensins; Blood Vessels; Blood flow; Bradycardia; Breathing; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Characteristics; Chronic; Continuous Positive Airway Pressure; Disease; Dyspnea; Economic Inflation; Environmental air flow; Enzymes; Exercise; Exercise Tolerance; Functional disorder; Gender; Genetic Polymorphism; Genotype; Heart; Heart Rate; Heart failure; Hyperpnea; Incidence; Ischemia; Left; Leg; Link; Lung; Measures; Mechanics; Muscle; Patients; Peptidyl-Dipeptidase A; Peripheral; Permeability; Plasma; Population; Reflex action; Regulation; Rehabilitation therapy; Relative (related person); Renin-Angiotensin System; Respiratory Muscles; Respiratory System; Rest; Shortness of Breath; Skeletal Muscle; Stroke Volume; System; Testing; Theft; Tidal Volume; Tissues; Ventricular; Work; base; cost; lung volume; neuroregulation; peripheral blood; pressure; pulmonary function; receptor; respiratory; response; thoracic pressure

DESCRIPTION (provided by applicant): The central theme of our proposal is to understand mechanisms of exercise intolerance in Chronic Heart Failure (CHF) and to ultimately use this information to help guide rehabilitation and medical management of this growing population. This is of importance because, the incidence of CHF increases 50-fold between the ages of 40 and 60 years and the disease is the nation's most rapidly growing cardiovascular disorder. Two specific aims focused on heart and lung interactions will be addressed. First, we will test the hypothesis that breathing during exercise influences cardiac function. We will test this by, a) examining the influence of transient and sustained increases in lung volume on cardiac function during exercise using continuous positive airway pressure, expiratory threshold loading and voluntary maneuvers, b) determining the effects of intra-thoracic pressure changes on cardiac output via loading and unloading the respiratory muscles using proportional assist ventilation during exercise, c) examine if a muscle chemosensitive reflex may stimulate ventilation in CHF greater than in controls by using post-exercise leg ischemia, and d) determining if the respiratory muscles "steal" blood flow from locomotor muscles during exercise by unloading respiratory muscles and measuring leg blood flow. Second, we will examine a neurohumoral basis for structural changes in the pulmonary system and altered exercise tolerance in CHF by examining a polymorphism of a key regulatory enzyme, angiotensin-converting enzyme (ACE, which exists in 2 forms, insertion-Il and deletion-DD alleles). We will test this by, a) determining if the activated renin-angiotensin system in CHF enhances ACE genotype related differences in pulmonary and cardiovascular function relative to controls, b) determining if the altered pulmonary function in the DD genotype of CHF patients is related to alterations in pulmonary vascular tone and permeability and independent of cardiac function c) examining if complete blockade of angiotensin-Il (A-Il) with A-Il receptor blockers will abolish genotype differences in the CHF subjects.

描述(由申请者提供)：我们提案的中心主题是了解慢性心力衰竭(CHF)中运动不耐受的机制，并最终使用这些信息来帮助指导这一不断增长的人口的康复和医疗管理。这一点很重要，因为CHF的发病率在40岁到60岁之间增加了50倍，而这种疾病是美国增长最快的心血管疾病。两个专注于心肺相互作用的具体目标将被解决。首先，我们将检验运动中的呼吸影响心脏功能的假设。我们将通过以下方法来测试这一点：a)使用持续正压、呼气阈值负荷和自愿动作来测试运动期间肺容量的短暂和持续增加对心功能的影响；b)通过运动期间使用比例辅助呼吸机加载和卸载呼吸肌来确定胸腔内压力变化对心输出量的影响；c)通过运动后腿部缺血来检查肌肉化学敏感性反射是否可以刺激CHF患者比对照组更大的通气量；以及d)通过卸载呼吸肌肉和测量腿部血流量来确定呼吸肌是否在运动时“窃取”运动肌肉的血流量。其次，我们将通过检测关键调节酶血管紧张素转换酶(ACE)的多态性来研究CHF中肺系统结构变化和运动耐量改变的神经体液基础。血管紧张素转换酶以两种形式存在，插入-Il和缺失-DD等位基因。我们将通过以下方法进行测试：a)确定CHF患者被激活的肾素-血管紧张素系统是否增强了与ACE基因相关的肺和心血管功能与对照组相比的差异；b)确定CHF患者DD基因型的肺功能改变是否与肺血管张力和通透性的改变有关并且独立于心功能；c)检查用A-Il受体阻滞剂完全阻断血管紧张素-Il(A-Il)是否会消除CHF患者中的基因差异。