Parasympathetic Control of Right Ventricular Function

副交感神经系统对心功能的多种指标具有显著的影响，然而，对介导迷走神经对心室功能抑制作用的心脏内禀神经元回路知之甚少。因此，本申请支持的总体目标是，在一定程度上定义猫心脏室性神经节的神经解剖学、功能和药理组织。我们将通过光显微神经解剖学逆行示踪方法定量定义源自单个神经节的神经末梢的投影场。此外，我们建议验证脑室神经节之间存在神经节间神经解剖回路的假设（就像我们在选定的心房神经节之间证明的那样），以协调/促进脑室的同步功能。我们将使用双标记超微结构免疫细胞化学方法进一步确定交感神经节后神经末梢在心脏内在神经系统副交感神经元控制中的潜在作用。我们假设在交感神经末梢和心室神经节内的内在心脏神经元之间存在轴-体突触、轴-树突突触和轴-轴突突触。我们假设单个脑室内神经节介导迷走神经节后对心脏选择性心室区域功能的控制，和/或影响心室再极化的电生理底物，而不同时改变心率、房室传导或心房再极化。对心室收缩力、心输出量、每搏量、射血分数等生理指标进行综合评价

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.