NEUROCIRCULATORY FUNCTION IN CHRONIC HEART FAILURE

慢性心力衰竭（CHF）状态下的标志性外周调节之一是多种神经-体液系统的激活，包括交感神经系统、肾素-血管紧张素系统和血管加压素系统。最初，这些改变对机体有益，有助于维持灌注压以提供足够的冠状动脉和脑血流。然而，长期以来，这些调整变得适得其反，并有助于严重CHF特征的心血管恶化的恶性循环。了解神经体液激活发生的机制对于制定合理的治疗策略至关重要。我们提出了一个新的项目来研究在CHF的情况下心血管反射功能改变的机制。我们召集了一组经验丰富的研究人员，他们的专业知识围绕循环的反射控制。在项目一中，dr。Zucker和Patel将研究中枢血管紧张素II （Ang II）和一氧化氮（NO）在实验性CHF家兔交感神经流出中的作用。重复练习对反射异常的改善作用也将被检查。在项目II中，dr。Patel和Pucker将研究NO和室旁核GABAnergic系统在CHF大鼠交感神经流出调节中的作用。项目三将由博士领导。舒尔茨，罗赞斯基和王。本项目的重点是外周化学反射及其对CHF家兔交感神经张力增强的贡献。化学感受器NO对化学反射传入成分的影响将被研究。增强的化学反射敏感性可能有助于CHF的交感神经兴奋。在项目四，博士。Wang， Pucker和Schultz将在犬CHF模型中研究心脏“交感神经传入”反射在交感神经流出调节中的作用。这种兴奋性反射在CHF中表现出增强的敏感性，可能是由中枢AII和NO的改变介导的。最后，在项目V中，dr。Sinoway和Leunberger将研究CHF患者的肌肉代谢反射。它们将确定运动肌肉的传入信号，该信号负责增强这种反射，以及运动对该信号的作用。微透析将用于CHF患者，以确定可能负责激活III型和IV型传入的各种物质的间质浓度。因此，项目I、II和IV将关注CHF的中枢异常。项目III、IV和V将关注传入异常。所有项目都独特地与心衰神经循环控制的中心主题相关。

One of the hallmark peripheral adjustments in the state of chronic heart failure (CHF) is activation of a variety of neuro-humoral systems, including the sympathetic nervous system, the renin-angiotensin system and the vasopressin system. Initially, these alterations are of benefit to the organism, helping to maintain perfusion pressure to provide adequate coronary and cerebral blood flow. However, chronically these adjustments become counter productive and contribute to the downward spiral of cardiovascular deterioration characteristic of severe CHF. Understanding the mechanisms by which neuro-humoral activation occurs is crucial to the development of rational strategies for the treatment of patients with CHF. We propose a new program project to investigate the mechanisms by which cardiovascular reflex function is altered in the setting of CHF. We have assembled a experienced group of investigators whose expertise revolved around the reflex control of the circulation. In project I, Drs. Zucker and Patel will investigate the role of central angiotensin II (Ang II) and nitric oxide (NO) in modulating sympathetic outflow in rabbits with experimental CHF. The ameliorating effects of repetitive exercises on reflex abnormalities will also be examined. In project II, Drs. Patel and Pucker will examine the role of NO and the GABAnergic system in the paraventricular nucleus on the modulation of sympathetic outflow in rats with CHF. Project III will be led by Drs. Schultz, Rozanski and Wang. This project is focused on the peripheral chemoreflex and its contribution to augmented sympathetic tone in rabbits with CHF. The involvement of alterations in chemoreceptor NO on the afferent component of the chemoreflex will be investigated. Enhanced chemoreflex sensitivity may contribute to sympatho-excitation in CHF. In project IV, Drs. Wang, Pucker and Schultz will investigate the role of the cardiac "sympathetic afferent" reflex in the modulation of sympathetic outflow in a canine model of CHF. This excitatory reflex exhibits enhanced sensitivity in CHF and may be mediated by alterations in central AII and NO. Finally, in Project V, Drs. Sinoway and Leunberger will examine the muscle metaboreflex in humans with CHF. They will determine the afferent signal from exercising muscle which is responsible for augmentation of this reflex and the role of exercise on this signal. Microdialysis will be used in patients with CHF to determine the interstitial concentrations of various substances which may be responsible for activating Type III and Type IV afferents. Thus projects, I, II and IV will be concerned with central abnormalities in CHF. Projects III, IV and V will be concerned with afferent abnormalities. All projects unique interrelate to the central theme of neuro-circulatory control in CHF.