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、肺和动脉压力感受反射 慢性心力衰竭动物模型中循环的控制 （高频）。 慢性心动过速将用于产生充血状态 高频。 该模型导致心脏扩张、收缩力降低、 肺水肿和运动不耐受。 具体来说，我们将 确定：1)交感神经的动脉压力反射控制 心力衰竭的清醒动物的活动以及压力感受反射是否 主要负责交感神经流出的慢性增加 在高频中。 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被消融，这种心力衰竭模型也是如此。 我们将把这些实验扩展到交感神经的直接测量 理论流出。 如果这些数据得到证实，那就意味着 公认的压力感受反射功能不良导致慢性增加的观念 心力衰竭中的交感神经流出不再成立。 2）如果增强输入 来自迷走神经肺传入神经（可能受到肺神经刺激） 水肿、肺顺应性或局部体液介质的变化） 部分，负责众所周知的压力反射敏感性的抑制 发生于HF。 该实验将在长期肺部进行 患有或不患有心力衰竭的去神经犬。 3）心脏的程度 心力衰竭时机械反射和化学反射发生改变。根据初步数据 我们假设反射来自无髓鞘 C 纤维 诱发慢性心力衰竭后，传入神经可能会增强。 4）如果 心力衰竭时心肺传入神经的敏感性发生改变。 记录将由肺部的迷走神经和交感神经纤维进行 以及来自假狗和高频狗的心脏。 我们将确定传入信号是否来自 心力衰竭犬的肺部对各种机械刺激反应正常 例如肺过度充气和肺充血。 研究将是 在肺水肿减轻之前和之后进行。 回应 化学刺激的这些结局也将在心衰狗身上进行检查。 我们将集中研究已知能够刺激的物质 C 纤维传入，例如前列腺素和缓激肽。 相似的 将对心脏传入进行实验。机械刺激 将包括升主动脉和腔静脉闭塞。 化学 刺激将包括冠状动脉内和局部应用 前列腺素、花生四烯酸和缓激肽。