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. Beta blockers, or drugs with beta blocking effects, are known to prevent sudden cardiac death. It was unclear if the cardiac nerves in the heart play only a passive role in the mechanisms of sudden death. To determine if nerve sprouting and neural remodeling occur after myocardial infarction, we performed immunocytochemical studies of cardiac nerves in explanted native hearts of transplant recipients. We found that there was a positive correlation between nerve density and a clinical history of ventricular arrhythmia. Encouraged 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), ventricular fibrillation (VF), and sudden cardiac death (SCD). The results showed that augmented myocardial sympathetic nerve sprouting through NGF infusion plus atrioventricular (AV) block and MI result in a 44% incidence (four of nine dogs) of SCD and a high incidence of VT in the chronic phase of MI. In contrast, none of the six dogs (with AV block and MI) without NGF infusion died suddenly or had frequent VT episodes. Based on these findings, we propose the nerve sprouting hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI results in nerve injury, followed by sympathetic nerve sprouting and regional (heterogeneous) myocardial hyperinnervation. The coupling between augmented sympathetic nerve sprouting with electrically remodeled myocardium results in VT, VF and SCD. Modification of nerve sprouting after MI may provide a novel opportunity for arrhythmia control.
Chen
P S
PS
Division of Cardiology, Department of Medicine, Cedars--Sinai Medical Center, Rm 5342, 8700 Beverly Blvd., Los Angeles, CA 90048-1865, USA. chenp@csmc.edu
Chen
L S
LS
Cao
J M
JM
Sharifi
B
B
Karagueuzian
H S
HS
Fishbein
M C
MC
D000818:Animals; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006801:Humans; D009203:Myocardial Infarction / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*