Parasympathetic Control of Right Ventricular Function

副交感神经控制右心室功能

• 批准号: 6966941
• 负责人: MARTHA ISABEL DAVILA-GARCIA
• 金额: $ 22.91万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6966941
• 关键词: cats; cholinergic receptors; cooperative study; electrocardiography; electrophysiology; heart electrical activity; heart function; heart innervation; heart pharmacology; heart ventricle; light microscopy; neuroanatomy; parasympathetic nervous system; vagus nerve

The parasympathetic nervous system exerts dramatic effects on multiple indices of cardiac function, however, very little is known about the Intrinsic cardiac neuronal circuits which mediate vagal cardioinhibitory effects on ventricular functions. The overall goal of this application for support is therefore, to define, in part, the neuroanatomical, functional, and pharmacological organization of ventricular ganglia within the cat heart. We will quantitatively define the projection field(s) of nerve terminals originating from Individual ganglia by light microscopic neuroanatomical retrograde tracing methods. Moreover, we propose to test the hypothesis that Inter-ganglionic neuroanatomical circuits exist between ventricular ganglia (like those we have demonstrated between selected atrial ganglia) in order to coordinate/facilitate the synchronized functioning of the ventricles. We will further determine the potential role of sympathetic postganglionic nerve terminals in the control of parasympathetic neurons within the intrinsic cardiac nervous system using dual labeling ultrastructural immunocytochemical methods. We hypothesize that there are axo-somatic, axo-dendritic and axo-axonic synapses between sympathetic nerve terminals and intrinsic cardiac neurons within ventricular ganglia. We hypothesize that individual intraventricular ganglia mediate the vagal postganglionic control of the function of selective ventricular regions of the heart, and/or the electrophysioiogical substrate influencing repolarization of the ventricles, without simultaneously modifying cardiac rate, atrioventricular conduction, or repolarization of the atria. Physiological evaluation of ventricular contractility, cardiac output, stroke volume, ejection fraction etc. will be determined by combined echocardiographic and computerized pressure-volume (PV) loop analysis. Changes in the electrophysiology of the atria and ventricles will also be determined in parallel EKG analyses. Pharmacological studies using nicotinic acetylcholine receptor (nAChR) subtype-selective agonist and antagonist drugs will define the characteristics of neuronal nAChRs in these ganglia. The proposed studies will:1) test significant new hypotheses regarding the light microscopic and ultrastructural organization of ventricular gangHa within the Intrinsic cardiac nervous system; 2) refine our understanding of the specific nAChRs subtypes used within these ganglia; and 3) clarify the specific physiological and/or electrophysiological functions which intraventricular ganglia exert on the heart. These data will be essential to the understanding of cardiac function in health and in disease.

副交感神经系统对心脏功能的多个指标产生显著影响，然而，关于介导迷走神经心脏抑制效应对心室功能的内在心脏神经元回路知之甚少。因此，本申请支持的总体目标是部分定义猫心脏心室神经节的神经解剖学、功能和药理学组织。我们将利用光学显微镜神经解剖学逆行追踪方法，定量地确定源自单个神经节的神经末梢的投射野。此外，我们建议测试的假设，即间神经节神经解剖电路之间存在的心室神经节（如我们所证明的选择心房神经节之间），以协调/促进心室的同步功能。我们将进一步确定交感节后神经末梢的潜在作用，在控制副交感神经元的内在心脏神经系统内使用双标记超微结构免疫细胞化学方法。我们推测在心室神经节内交感神经终末与心内神经元之间存在轴-体、轴-树和轴-轴突触。我们假设，个别室内神经节介导迷走神经节后控制的功能，选择性心室区域的心脏，和/或电生理基板影响复极的心室，而不同时修改心率，房室传导，或复极的心房。心室收缩力、心输出量、每搏输出量、射血分数等的生理学评价将通过联合 超声心动图和计算机化压力-容积（PV）环分析。心房和心室电生理学的变化也将在平行的心电图分析中确定。使用烟碱乙酰胆碱受体（nAChR）亚型选择性激动剂和拮抗剂药物的药理学研究将定义这些神经节中神经元nAChR的特征。拟议的研究将：1）测试有关内在心脏神经系统中心室神经节的光镜和超微结构组织的重要新假设; 2）完善我们对这些神经节中使用的特定nAChR亚型的理解; 3）阐明心室内神经节对心脏发挥的特定生理和/或电生理功能。这些数据将是必不可少的， 了解健康和疾病中的心脏功能。