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.
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