Parasympathetic Control of Right Ventricular Function

副交感神经系统对心功能的多项指标有显著影响，但对迷走神经抑制心功能的内在心脏神经回路知之甚少。因此，这项支持申请的总体目标是，部分定义猫心脏内脑室神经节的神经解剖学、功能和药理学组织。我们将用光镜下神经解剖逆行示踪法定量确定发自单个神经节的神经末梢投射野(S)。此外，我们建议检验在室神经节之间存在节间神经解剖环路的假说(就像我们已经证明的在选定的房神经节之间存在的神经环)，以协调/促进脑室的同步功能。我们将使用双重标记的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控制心脏固有神经系统内的副交感神经元中的潜在作用。我们推测在交感神经末梢和心脏内源性神经元之间存在轴体突触、轴树突触和轴轴突触。我们假设，单个脑室内神经节参与迷走神经节后控制心脏选择性室区的功能，和/或影响脑室复极的电生理底物，而不同时改变心率、房室传导或心房复极。对心室收缩能力、心输出量、每搏输出量、射血分数等的生理学评估将通过联合 超声心动图和计算机化的压力-容量(PV)环分析。房室电生理的改变也将在平行的EKG分析中确定。使用烟碱型乙酰胆碱受体(NAChR)亚型选择性激动剂和拮抗剂药物的药理学研究将确定这些神经节中nAChR的特征。拟议的研究将：1)检验关于心脏固有神经系统内脑室神经节Ha的光镜和超微结构组织的新的重要假说；2)加深我们对这些神经节中使用的特定nAChRs亚型的理解；3)阐明脑室内神经节对心脏施加的特定生理和/或电生理功能。这些数据将是 了解健康和疾病中的心脏功能。

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.