Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death
Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death
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DOI：
10.1016/s0008-6363(00)00308-4
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发表时间：
2001-05-01
影响因子：
10.8
通讯作者：
Fishbein, MC
中科院分区：
文献类型：
--
作者：
Chen, PS;Chen, LS;Fishbein, MC
本文旨在对心源性猝死的神经萌芽假说进行综述。众所周知，交感神经刺激在心源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日变化。-受体阻滞剂，或具有-阻断作用的药物，已知可预防心源性猝死。目前尚不清楚心脏中的心神经是否在猝死机制中仅起被动作用。为了确定心肌梗死后是否会出现神经萌芽和神经重塑，我们对移植受者的移植原生心脏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，我们在狗身上进行了一项研究，以确定神经生长因子（NGF）输注到左星状神经节是否会促进室性心动过速（VT）、心室颤动（VF）和心源性猝死（SCD）的发展。结果显示，在心肌梗死慢性期，通过NGF输注增强的心肌交感神经萌芽加房室（AV）阻滞和心肌梗死可导致44%（9只犬中4只）的SCD发生率和较高的VT发生率，而未输注NGF的6只（AV阻滞和心肌梗死）犬均无突然死亡或频繁的VT发作。基于这些发现，我们提出了室性心律失常和SCD的神经萌芽假说。假设认为心肌梗死导致神经损伤，随后是交感神经萌芽和局部（异质）心肌神经过度支配。增强的交感神经萌芽与电重构心肌之间的耦合导致VT、VF和SCD。心肌梗死后神经萌芽的改变可能为心律失常的控制提供新的机会。(C) 2001 Elsevier Science B.V.版权所有
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)I 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. (C) 2001 Elsevier Science B.V. All rights reserved.