Heart-brain interactions in cardiac arrhythmias: Role of the autonomic nervous system
ABSTRACT
The autonomic nervous system plays an important role in the genesis of ventricular arrhythmias and sudden cardiac death. Evidence is substantial for a neural component in sudden cardiac death. Sympathetic nerve sprouting and regional myocardial hyperinnervation following myocardial injury promote cardiac arrhythmia and sudden cardiac death through several potential mechanisms. Modulating autonomic tone is a potential method to reduce the risk of ventricular arrhythmias. Thoracic spinal cord stimulation is showing promise as a treatment for refractory angina. In addition, spinal cord stimulation has protected against ventricular tachycardia/ventricular fibrillation in animal models of postinfarction heart failure.
PHARMACOLOGIC SYMPATHETIC BLOCKADE
Inhibiting sympathetic activity pharmacologically reduces the incidence of sudden cardiac death in patients with heart failure. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), the aldosterone inhibitor eplerenone was associated with a clear reduction in sudden cardiac arrest in patients with acute MI complicated by left ventricular dysfunction.13 Beta-blockers and angiotensin-converting enzyme inhibitors have had the same effect. These findings indicate that adverse electrophysiologic consequences from sympathetic stimulation may contribute to the development of a pro-arrhythmic substrate, and that antagonizing sympathetic activation can reduce the extent of adverse electrical remodeling to reduce the risk of sudden cardiac death.
SPINAL CORD STIMULATION
Acute spinal cord stimulation
The possibility of using spinal cord stimulation to modulate cardiac arrhythmias is intriguing, as electrodes introduced paraspinally may activate nerves that could affect sympathetic function. In Europe, spinal cord stimulation is already approved for treatment of patients with intractable angina and end-stage coronary disease.
The mechanism responsible for elimination of angina pectoris via carotid sinus massage is presumably an increase in vagal activity to the heart. In a study of whether thoracic spinal cord stimulation eliminates angina pectoris via a vagal mechanism, Olgin et al confirmed that spinal cord stimulation at the T1-T2 segments enhanced parasympathetic activity and that this action is mediated via the vagus.14 These findings suggest that thoracic spinal cord stimulation may protect against ventricular arrhythmias through its effect on autonomic tone.
This suggestion led to the development of a canine model of spontaneous ventricular arrhythmias to investigate the mechanisms responsible for ventricular arrhythmias related to acute myocardial ischemia in the setting of healed MI.15 An infarct was produced via occlusion of the left anterior descending coronary artery and a permanent ventricular pacemaker was placed. After a 2-week recovery period, heart failure was induced by continuous rapid ventricular pacing for 2 to 3 weeks. Transient myocardial ischemia was induced by transient occlusion of the proximal left circumflex coronary artery. Seventy-two percent of dogs surviving the rapid pacing period developed VT/VF during acute left circumflex artery occlusion or within 1 to 2 minutes thereafter.
The effect of thoracic spinal cord stimulation applied at the dorsal T1-T2 segments was studied on the surviving dogs.16 Spinal cord stimulation reduced the occurrence of VT/VF from 59% to 23%.
Another study examined the effect of intrathecal clonidine, an alpha-2 antagonist that reduces concentrations of catecholamines, on ventricular arrhythmias in the canine model.17 Ischemia-induced VT/VF occurred in 9 of 12 dogs before administration of intrathecal clonidine in contrast to only 3 of 12 dogs after clonidine administration, a degree of efficacy similar to that with spinal cord stimulation.
Chronic spinal cord stimulation
Studies of the effects of chronic thoracic spinal cord stimulation on ventricular function and ventricular arrhythmias in a canine postinfarction heart failure model have recently been completed, and the results will be published in the near future.18
CONCLUSIONS
Sudden cardiac death continues to be a major health problem in Western countries. Many approaches have been explored in attempting to reduce this modern-day plague.19 A better understanding of the risks, mechanisms, and treatments is required.20 An animal model has demonstrated that acute modulation of autonomic tone with thoracic spinal cord stimulation or intrathe-cal clonidine reduces susceptibility to ischemic ventricular arrhythmias, presumably via a sympatholytic mechanism. Modulation of autonomic tone—sympatholytic, vagomimetic, or both—may play a significant role in protecting against spontaneous and ischemic ventricular tachyarrhythmias.
