The electrophysiological effects of nicotinic and electrical stimulation of intrinsic cardiac ganglia in the absence of extrinsic autonomic nerves in the rabbit heart.

BACKGROUND: The intrinsic cardiac nervous system (ICNS) is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function. OBJECTIVE: To provide a picture of the neurotransmitter/neuromodulator profile of the rabbit ICNS and determine the action of spatially divergent ganglia on cardiac electrophysiology. METHODS: Nicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff perfused rabbit heart. Functional effects on sinus rate and atrioventricular conduction were measured. Immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH) and/or neuronal nitric oxide synthase (nNOS) was performed on whole-mount preparations. RESULTS: Stimulation within all ganglia produced either bradycardia, tachycardia or a biphasic brady-tachycardia. Electrical stimulation of the right atrial (RA) and right neuronal cluster (RNC) regions produced the greatest chronotropic responses. Significant prolongation of atrioventricular conduction (AVC) was predominant at the pulmonary vein-caudal vein region (PVCV). Neurons immunoreactive (IR) only for ChAT, or TH or nNOS were consistently located within the limits of the hilum and at the roots of the right cranial and right pulmonary veins. ChAT-IR neurons were most abundant (1946±668 neurons). Neurons IR solely for nNOS were distributed within ganglia. CONCLUSION: Stimulation of intrinsic ganglia, shown to be of phenotypic complexity but predominantly of cholinergic nature, indicates that clusters of neurons are capable of independent selective effects on cardiac electrophysiology, therefore providing a potential therapeutic target for the prevention and treatment of cardiac disease.