Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction

Abstract

Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control.

Figure 1

Anatomy and distribution of autonomic innervation of the heart. The cardiac parasympathetic nerves come from parasympathetic neurons located in the cardiac fat pads whose preganglionic fibers are carried within the vagus nerve. The cardiac sympathetic nerves come from the paravertebral ganglia and project from the base of the heart into the myocardium.

Figure 2

Sympathetic nerve remodeling increases the propensity for cardiac arrhythmias after myocardial infarction. Myocardial infarction induced NGF transported retrogradely to left (and right) stellate ganglion and other injury signals such as increased afferent nerve traffic lead to anatomic remodeling within the stellates. Increased efferent nerve signals back to the heart and promotes nerve sprout which together with electrical as well as β-adrenergic receptor remodeling increases the propensity for malignant ventricular arrhythmias. It is not clear whether higher nervous centers also regulate this process. Solid lines represent known pathways; dotted lines represent unknown.