The Role of the Autonomic Nervous System in Sudden Cardiac Death

Abstract

The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

Are Changes in Heart Rate Variability in Middle‐Aged and Older People Normative or Caused by Pathological Conditions? Findings From a Large Population‐Based Longitudinal Cohort Study

“…This may include disturbed cardiac acetylcholine release response to stimulation,39 decreases in muscarinic receptor activity,40 and reductions in M2 muscarinic receptor density with aging,41 all of which have been shown to decrease with aging in clinical trials. Loss of protective vagal reflexes seems to hinder physical and psychological functioning and capacity to respond flexibly to efferent stimuli, resulting in increased vulnerability to the diseases2, 42 that are often prevalent at older ages 43…”

“…One indicator that seems to play a pivotal role is dysfunction of the autonomic nervous system. Specifically, increased sympathetic and/or decreased parasympathetic activity has been associated with increased risk for a number of cardiac outcomes such as sudden cardiac death, heart failure, ventricular arrhythmias, or hypertension 2, 3. Heart rate variability (HRV) is a valid noninvasive technique for estimating the characteristics of the autonomic nervous system and for quantifying modulation of the sympathetic and parasympathetic inputs 4, 5.…”

Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats

“…Both of these catecholamines have been shown to exert a direct toxic effect, leading to myocyte lesion and apoptosis 23,24 . Norepinephrine binds to myocardial β-adrenergic receptors, which increases the levels of cyclic adenosine monophosphate (cAMP), by the activation of adenylate cyclase 25 . Elevated levels of cAMP precede an influx of calcium inside the myocyte by the phosphorylation of L-type calcium channels by the protein kinase A 25 .…”

Sudden cardiac death in the young: cytokines and pathways

“…In inherited arrhythmia disorders, sympathetic stimulation implicates in ventricular tachyarrhythmias and SCDs. In the animals susceptible to sudden death, modulation of the autonomic tone may increase cardiac vagal activity and reduce the risk for VF and SCDs (47).…”