Chen P S, Chen L S, Cao J M, Sharifi B, Karagueuzian H S, Fishbein M C
Division of Cardiology, Department of Medicine, Cedars--Sinai Medical Center, Rm 5342, 8700 Beverly Blvd., Los Angeles, CA 90048-1865, USA.
Cardiovasc Res. 2001 May;50(2):409-16. doi: 10.1016/s0008-6363(00)00308-4.
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.
本文旨在综述心脏性猝死的神经发芽假说。众所周知，交感神经刺激在心脏性猝死的发生中起重要作用。例如，心肌梗死患者的猝死率存在昼夜变化。β受体阻滞剂或具有β阻滞作用的药物可预防心脏性猝死。目前尚不清楚心脏中的心脏神经在猝死机制中是否仅起被动作用。为了确定心肌梗死后是否发生神经发芽和神经重塑，我们对移植受者离体天然心脏中的心脏神经进行了免疫细胞化学研究。我们发现神经密度与室性心律失常的临床病史之间存在正相关。受这些结果的鼓舞，我们在犬类中进行了一项研究，以确定向左星状神经节注入神经生长因子（NGF）是否会促进室性心动过速（VT）、室颤（VF）和心脏性猝死（SCD）的发生。结果显示，通过注入NGF加上房室（AV）阻滞和心肌梗死增强心肌交感神经发芽，在心肌梗死慢性期导致SCD发生率为44%（9只犬中有4只），VT发生率较高。相比之下，6只未注入NGF的犬（伴有AV阻滞和心肌梗死）均未突然死亡或频繁发生VT发作。基于这些发现，我们提出了室性心律失常和SCD的神经发芽假说。该假说指出，心肌梗死导致神经损伤，随后是交感神经发芽和局部（异质性）心肌去神经支配过度。增强的交感神经发芽与电重塑心肌之间的耦合导致VT、VF和SCD。心肌梗死后神经发芽的改变可能为心律失常的控制提供新的机会。
