Sudden infant death syndrome is the leading cause of death in infancy, but its pathophysiological mechanism has been elusive. Sudden death in adults is a common phenomenon, but the etiology in many cases remains unknown at autopsy. We hypothesize that maladaptive sympathetic bias is the explanatory mechanism that links many cases of sudden demise among adults and infants as companion syndromes. Normally, sympathetic response occurs as an adaptation to physiologic demands of the body through various autonomic reflex arcs such as chemoreceptors. Sympathetic response can become chronic and maladaptive when the normal sympathetic response fails to correct the precipitating physiologic trigger, leading to chronic activation of autonomic reflex arcs. In conditions such as infant sleep apnea or adult heart failure, a pernicious cycle of sympathetic bias may result. Chronic sympathetic bias increases susceptibility to sudden fatal arrhythmias, QT-related and otherwise, in the setting of an exaggerated adrenergic challenge. Examples of such adrenergic stressors include trauma, hypoxia, hypercapnia, acidosis, sleep arousal, illness, medical procedures, and physical activity, all of which have associations with sudden death. Our hypothesis may not only help explain the survival benefits of drugs such as beta-blockers and devices such as synchronization therapy, but also portend new application of similar therapies for many conditions of sympathetic bias.
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