Novel insights into the role of the sympathetic nervous system in cardiac arrhythmogenesis.
It has long been recognized that increased sympathetic nerve activity during physiologic stress (exercise, swimming, emotion, arousal, loud noise, etc.) has profound influences on the electrical and contractile functions of the heart. In the severely predisposed heart, these stressors may lead to ventricular tachyarrhythmias and sudden death. Still little is known about the temporal relationship between instantaneous autonomic nerve activity and arrhythmias. There is a large variety of autonomically-driven arrhythmias, from serious ventricular tachycardia in pathological conditions to single supraventricular and ventricular extrasystolic beats in the healthy heart. The latter are considered harmless if occurring at low frequency. In the atria, mounting data indicate the presence of a sophisticated network of ganglionated plexi with major influences on cardiac function. The ablation of multiple such ganglia can suppress pulmonary vein potentials and atrial fibrillation. At the cellular level, recent studies have focused on the spatiotemporal details of cyclic nucleotide signaling influencing ion channel function during neurohumoral stimulation. We have come to understand that sarcolemmal ion channels and other electrogenic transporters are macromolecular complexes that interact with structural elements (other than the phospholipid bilayer) to promote regionalization and targeting by regulatory proteins. Compartmentation of these regulatory proteins in subdomains of the myocyte is increasingly recognized and thought to segregate the functional (including electrogenic) responses induced by different neuromediators and hormones. In this article, contemporary issues are discussed regarding arrhythmias that are triggered by influences from the neurocardiac interface, covering the field from the molecular genetic to the intact integrated level. Actual questions are listed per topic, and viewpoints are expressed.
Volders
Paul G A
PG
Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands. p.volders@cardio.unimaas.nl
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac; D005728:Ganglia, Sympathetic / Q000503:physiopathology; D006325:Heart Atria / Q000294:innervation / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D017725:Ventricular Pressure
D007473:Ion Channels; D051657:KCNQ1 Potassium Channel; D011943:Receptors, Adrenergic, beta