Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death

The purpose of this article is to review the nerve sprouting hypothesis of sudden cardiac death. It is known that sympathetic stimulation is important in the generation of sudden cardiac death. For example, there is a diurnal variation of sudden death rate in patients with myocardial infarction. Bet a blockers, or drugs with beta blocking effects, are known to prevent sudde n cardiac death. It was unclear if the cardiac nerves in the heart play onl y a passive role in the mechanisms of sudden death. To determine if nerve s prouting and neural remodeling occur after myocardial infarction, we perfor med immunocytochemical studies of cardiac nerves in explanted native hearts of transplant recipients. We found that there was a positive correlation b etween nerve density and a clinical history of ventricular arrhythmia, Enco uraged by these results, we performed a study in dogs to determine whether or not nerve growth factor (NGF) infusion to the left stellate ganglion can facilitate the development of ventricular tachycardia (VT)I ventricular fi brillation (VF), and sudden cardiac death (SCD). The results showed that au gmented myocardial sympathetic nerve sprouting through NGF infusion plus at rioventricular (AV) block and MI result in a 44% incidence (four of nine do gs) of SCD and a high incidence of VT in the chronic phase of MI, In contra st, none of the six dogs (with AV block and MI) without NGF infusion died s uddenly or had frequent VT episodes, Based on these findings, we propose th e nerve sprouting hypothesis of ventricular arrhythmia and SCD. The hypothe sis states that MI results in nerve injury, followed by sympathetic nerve s prouting and regional (heterogeneous) myocardial hyperinnervation. The coup ling between augmented sympathetic nerve sprouting with electrically remode led myocardium results in VT, VF and SCD. Modification of nerve sprouting a fter MI may provide a novel opportunity for arrhythmia control. (C) 2001 El sevier Science B.V. All rights reserved.