Myths and realities of the cardiac vagus

Abstract

There is continuing belief that cardiac parasympathetic postganglionic fibres are sparse or absent from the ventricles. This review of the literature shows that the supposition is a myth. Early studies considered that fine silver-stained fibres coursing amongst ventricle myocardial cells were most likely cardiac parasympathetic postganglionic fibres. The conclusions were later supported by acetyl cholinesterase staining using a method that appeared not to be associated with noradrenaline nerve fibres. The conclusion is critically examined in the light of several recent histological studies using the acetyl cholinesterase method and also a more definitive technique (CHAT), that suggest a widespread location of parasympathetic ganglia and a relatively dense parasympathetic innervation of ventricular muscle in a range of mammals including man. The many studies demonstrating acetylcholine release in the ventricle on vagal nerve stimulation and a high density of acetylcholine M 2 receptors is in accord with this as are tests of ventricular performance from many physiological studies. Selective control of cardiac functions by anatomically segregated parasympathetic ganglia is discussed. It is argued that the influence of vagal stimulation on ventricular myocardial action potential refractory period, duration, force and rhythm is evidence that vagal fibres have close apposition to myocardial fibres. This is supported by clear evidence of accentuated antagonism between sympathetic activity and vagal activity in the ventricle and also by direct effects of vagal activity independent of sympathetic activity. The idea of differential control of atrial and ventricular physiology by vagal C and vagal B preganglionic fibres is examined as well as differences in chemical phenotypes and their function. The latter is reflected in medullary and supramedullary control. Reference is made to the importance of this knowledge to understanding the normal physiology of cardiac autonomic control and significance to pathology.

Cardiac Resynchronization Therapy Restores Sympathovagal Balance in the Failing Heart by Differential Remodeling of Cholinergic Signaling

“…This question is germane to the effect of vagal nerve stimulation (VNS) in HF 14 . Under normal resting conditions, cholinergic signaling is the predominant autonomic influence on the heart 9 . In the continued presence of cholinergic stimulation, CaT and SS responses to β-adrenergic stimulation were markedly depressed in DHF (by 42% and 56%) and less inhibited in normal and CRT myocytes (Fig.…”

“…While mechanisms leading to depressed β-adrenergic signaling have been studied extensively, far less is known about concurrent functional alterations in cholinergic (parasympathetic/muscarinic) signaling or its role in the HF phenotype 9 . Evidence from animal models 10, 11 and ongoing clinical trials 12–14 suggests modulating cholinergic activity and restoring sympathovagal balance has salutary effects in HF, but the underlying molecular mechanisms have not been established 9 . The effect of CRT on cholinergic signaling is unexplored.…”

The Roles of Gβγ and Gα in Gating and Regulation of GIRK Channels

“…Nevertheless, GIRK1's RNA is as abundant as the major G protein-independent inward rectifier, IRK1 (Kir2.1) in the ventricle (Marionneau et al, 2005). Accordingly, recent studies indicate a role for GIRK in shaping the action potential (AP) both in atrium and ventricle (Beckmann et al, 2008;Coote, 2013;Liang et al, 2014;Yang et al, 2010). The majority of cardiac GIRK channels are GIRK1/GIRK4 (GIRK1/4) heterotetramers (Bettahi, Marker, Roman, & Wickman, 2002;Nikolov & Ivanova-Nikolova, 2004a, 2004bYamada et al, 1998).…”

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation

“…The autonomic imbalance after MI impairs the angiogenesis in infarcted heart due to the decreased expressions of the α7-nicotinic acetylcholine (ACh) receptors (α7-nAChR) in MI-heart [7,8]. Indeed, vagal innervation of the conduction system and coronary vessels in heart [9] and the increased ACh concentration in left ventricular and circulation are observed when exposed to VNS [2,[10][11][12][13]. Since VNS mainly promotes α7-nAChR and m3-AChR expression in ischemia-reperfusion heart [14], activation of either α7-nAChR or m3-AChR by ACh may mediate VNS-induced angiogenesis in infarcted heart.…”