ViewpointNovel insights into the role of the sympathetic nervous system in cardiac arrhythmogenesis
Section snippets
The atria
The heart is a sensory organ with an intrinsic nervous system that is so extensive and sophisticated that it readily qualifies as a “little brain.”1 Through a complex hierarchy of feedback control circuits, sensory afferent and adrenergic and cholinergic efferent neurons communicate in ganglia. These reside in the heart (intrinsic cardiac ganglia) and outside the heart in the chest cavity (intrathoracic extracardiac ganglia). At least 7 regions with intrinsic ganglia have been identified in the
Current questions
Many questions emerge from the insights contained in the previous sections. To what extent, and in which balance, can autonomic stimulation of local versus remote ganglionated plexi determine the focal initiation of atrial tachycardias, including AF, in the human heart? Which anatomic and/or genetic variations exist among patients that predispose to atrial autonomic hypersensitivity or bluntness? Does autonomic remodeling contribute to the domestication of AF, and if so, how is neurophysiology
Current questions
To what extent, and in which balance, is sympathetic stimulation of the ventricles dictated by extracardiac versus intracardiac ganglia? Which are the extremes of ventricular autonomic innervation among normal human individuals?
It has recently been found that autonomic regulation itself is an arrhythmia risk modifier that can be genetically determined.34 This raises the question of which genetic variants of autonomic neural function, receptors,35 and neurotransmitters36 exist that can influence
Current questions
With the advances of molecular–genetic techniques and fluorescence microscopy, the compartmentation of signal proteins in subdomains of the cardiac myocyte is increasingly recognized. This compartmentation is thought to segregate the functional (including electrogenic) responses induced by different neuromediators and hormones. A major question is to what extent compartmentalized segregation of autonomic signal pathways is altered by cardiac overload. In hypertrophied cardiac myocytes from rats
Acknowledgments
Roel L. H. M. G. Spätjens, BSc, Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands, assisted in the figure making.
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Supported by a Vidi grant from the Netherlands Organization for Scientific Research (ZonMw 91710365).