CARDIOPULMONARY REFLEXES IN HEART FAILURE

心力衰竭时的心肺反射

• 批准号: 2218995
• 负责人: Irving H Zucker
• 金额: $ 20.16万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2218995
• 关键词: CARDIOPULMONARY; REFLEXES; HEART; FAILURE

This project will examine cardiac, pulmonary and arterial baroreflex control of the circulation in an animal model of chronic heart failure (HF). Chronic tachycardia will be used to produce a state of congestive HF. This model results in cardiac dilation, reduced contractility, pulmonary edema and exercise intolerance. Specifically, we will determine: 1) the arterial baroreflex control of sympathetic nerve activity in conscious animals with HF and whether or not the baroreflex is primarily responsible for the chronic increase in sympathetic outflow in HF. Preliminary data suggests that plasma norepinephrine increases in this model of HF even if the arterial baroreceptors have been ablated. We will extend these experiments to the direct measurements of sympa- thetic outflow. If these data are confirmed it would mean that the accepted notion of poor baroreflex function causing a chronic increase in sympathetic outflow in HF is no longer tenable. 2) If augmented input from vagal pulmonary afferents (which may be stimulated by pulmonary edema, changes in lung compliance or local humoral mediators) are, in part, responsible for the depression in baroreflex sensitivity known to occur in HF. This experiment will be carried out in chronically lung denervated dogs with and without HF. 3) The extent to which cardiac mechano- and chemoreflexes are altered in HF. Based on preliminary data we hypothesize that reflexes emanating from unmyelinated C-fiber afferents may be enhanced following the induction of chronic HF. 4) If the sensitivity of cardiac and pulmonary afferents are altered in HF. Recordings will be made from vagal and sympathetic fibers from the lungs and the heart from sham and HF dogs. We will determine if afferents from the lungs of dogs with HF respond normally to various mechanical stimuli such as pulmonary hyperinflation and lung congestion. Studies will be carried out before and after reduction of pulmonary edema. The response of these endings to chemical stimuli also will be examined in HF dogs. We will concentrate in these studies on substances known to stimulate C-fiber afferents, such as prostaglandins and bradykinin. Similar experiments will be carried out for cardiac afferents. Mechanical stimuli will include ascending aortic and vena caval occlusions. Chemical stimuli will include intracoronary and topical application of prostaglandins, arachidonic acid and bradykinin.

该项目将检查心脏，肺和动脉降压 控制慢性心力衰竭动物模型中的循环 （HF）。 慢性心动过速将用于产生充血状态 HF。 该模型导致心脏扩张，收缩性降低， 肺水肿和运动不耐受。 具体来说，我们会的 确定：1）交感神经的动脉压力反射控制 具有HF的有意识动物的活动以及是否降压 主要负责交感神经流出的慢性增长 在HF中。 初步数据表明血浆去甲肾上腺素增加 即使动脉压力感受器已经烧毁，这种HF的模型也是如此。 我们将将这些实验扩展到Sympa-的直接测量 thetic流出。 如果确认这些数据，则意味着 公认的不良屈光功能的概念，导致慢性增加 HF中的同情流出不再是可行的。 2）如果增强输入 来自迷走神经肺传入（可能由肺部刺激 水肿，肺合规或当地体液介质的变化）在 一部分，负责已知的压力反射灵敏度的抑郁症 发生在HF中。 该实验将在慢性肺中进行 带有和没有HF的狗被剥夺的狗。 3）心脏的程度 在HF中，机械和化学反射变化。基于初步数据 我们假设从无髓的C纤维产生的反射 慢性HF诱导后，可能会增强传入。 4）如果 心脏和肺传入的敏感性在HF中发生了改变。 录音将由迷走神经和同情纤维制成 以及假狗和HF狗的心。 我们将确定是否来自 HF的狗的肺正常反应于各种机械刺激 例如肺部过度充气和肺部充血。 研究将是 肺水肿还原之前和之后进行。 反应 在HF犬中，还将检查这些化学刺激的结局。 我们将专注于已知的刺激物质的研究 C纤维传入，例如前列腺素和心动激肽。 相似的 将针对心脏传入进行实验。机械刺激 将包括升高主动脉和静脉腔阻塞。 化学 刺激将包括冠状动脉内和局部应用 前列腺素，花生四烯酸和心动激肽。