The heart's ‘little brain’ controlling cardiac function in the rabbit

Abstract

New Findings•What is the topic of this review?The topic of the review is the intrinsic cardiac nervous system in the rabbit.•What advances does it highlight?The anatomy of rabbit intrinsic ganglia is similar to that of other species, including humans. Immunohistochemistry confirms the presence of cholinergic and adrenergic neurones, with a striking arrangement of neuronal nitric oxide synthase-positive cell bodies. Activation of atrial ganglia produces effects on local and remote regions.Heart disease is a primary cause of mortality in the developed world, and it is well recognized that neural mechanisms play an important role in many cardiac pathologies. The role of extrinsic autonomic nerves has traditionally attracted the most attention. However, there is a rich intrinsic innervation of the heart, including numerous cardiac ganglia (ganglionic plexuses), that has the potential to affect cardiac function independently as well as to influence the actions of the extrinsic nerves. To investigate this, an isolated, perfused, innervated rabbit Langendorff heart preparation was considered the best option. Although ganglionic plexuses have been well described for several species, there was no full description of the anatomy and histochemistry of rabbit hearts. To this end, rabbit intrinsic ganglia were located using acetylcholinesterase histology (n = 33 hearts). This revealed six generalized ganglionic regions, defined as a left neuronal complex above the left pulmonary vein, a right neuronal complex around the base of right cranial vein, three scattered in the dorsal right atrium and a region containing numerous ventricular ganglia located on the conus arteriosus. Using immunohistochemistry, neurons were found to contain choline acetyltransferase or tyrosine hydroxylase and/or neuronal nitric oxide synthase in differing amounts (choline acetyltransferase > tyrosine hydroxylase > neuronal nitric oxide synthase). The function of rabbit intrinsic ganglia was investigated using a bolus application of nicotine or electrical stimulation at each of the above sites whilst measuring heart rate and atrioventricular conduction. Nicotine applied to different ganglionic plexuses caused a bradycardia, a tachycardia or a mixture of the two, with the right atrial plexus producing the largest chronotropic responses. Electrical stimulation at these sites induced only a bradycardia. Atrioventricular conduction was modestly changed by nicotine, the main response being a prolongation. Electrical stimulation produced significant prolongation of atrioventricular conduction, particularly when the right neuronal complex was stimulated. These studies show that the intrinsic plexuses of the heart are important and could be crucial for understanding impairments of cardiac function. Additionally, they provide a strong basis from which to progress using the isolated, innervated rabbit heart preparation.

Principles of Safety Pharmacology

“…The isolated heart is free of extrinsic nerves (but does contain a rich intrinsic innervation of ganglionic plexuses; see Brack 2014) and circulating systemic hormonal factors as well as variation in haemodynamics that may alter drug activities. inotropic and lusitropic effects) and electrical properties of the heart ; Clements-Jewery and Curtis 2014).…”

Macrophages and cellular immunity in Drosophila melanogaster

“…In vertebrates, the nature and regulation of tissue macrophage local microenvironments remain unknown. However, the anatomical juxtaposition of self-renewing macrophages and local populations of peripheral neurons, such as observed in the skin [47, 48] heart [49–51], and pancreas [52], suggest that similar regulatory relationships may exist.…”

The heart is lost without the brain – the autonomic perspective

“…The intrinsic nerve cell bodies are grouped in ganglia or ganglionic plexuses that are widely distributed over the cardiac chambers, giving rise to the network of intrinsic nerves. During his talk, Brack (2015) highlighted that the neurons in the ganglionic plexuses display immunoreactivity not only for choline acetyltransferase but also for tyrosine hydroxylase and neuronal nitric oxide synthase. This would suggest that cardiac ganglia are not merely relay stations for parasympathetic input but are complex structures containing both Introduction parasympathetic and sympathetic nerves that are therefore capable of significantly influencing cardiac function in health and disease.…”