Table_1_Vagus Nerve Stimulation in Early Stage of Acute Myocardial Infarction Prevent Ventricular Arrhythmias and Cardiac Remodeling.XLS

Aims: To evaluate whether low level left vagus nerve stimulation (LLVNS) in early stage of myocardial infarction (MI) could effectively prevent ventricular arrhythmias (VAs) and protect cardiac function, and explore the underlying mechanisms.
Methods and Results: After undergoing implantable cardioverter defibrillators (ICD) and left cervical vagal stimulators implantation and MI creation, 16 dogs were randomly divided into three groups: the MI (n = 6), MI+LLVNS (n = 5), and sham operation (n = 5) groups. LLVNS was performed for 3 weeks. VAs, the left ventricular function, the density of the nerve fibers in the infarction area and gene expression profiles were analyzed. Compared with the MI group, dogs in the MI+LLVNS group had a lower VAs incidence (p < 0.05) and better left ventricular function. LLVNS significantly inhibited excessive sympathetic nerve sprouting with the evidences of decreased density of TH, GAP43 and NF positive nerves (p < 0.05). The gene expression profiling found a total of 206 genes differentially expressed between MI+LLVNS and MI dogs, mainly involved in cardiac tissue remodeling, cardiac neural remodeling, immune response and apoptosis. These genes, including 55 up-regulated genes and 151 down-regulated genes, showed more protective expressions under LLVNS.
Conclusions: This study suggests that LLVNS was delivered without altering heart rate, contributing to reduced incidences of VAs and improved left ventricular function. The potential mechanisms included suppressing cardiac neuronal sprouting, inhibiting excessive sympathetic nerve sprouting and subduing pro-inflammatory responses by regulating gene expressions from a canine experimental study.

研究目的：评估心肌梗死（myocardial infarction, MI）早期实施低强度左迷走神经刺激（low level left vagus nerve stimulation, LLVNS）能否有效预防室性心律失常（ventricular arrhythmias, VAs）并保护心功能，同时探究其潜在作用机制。

方法与结果：16只犬在完成植入式心律转复除颤器（implantable cardioverter defibrillators, ICD）、颈左侧迷走神经刺激器植入以及心肌梗死造模后，被随机分为3组：心肌梗死组（MI组，n=6）、MI+LLVNS组（n=5）以及假手术组（n=5）。LLVNS干预持续3周。随后对室性心律失常、左心室功能、梗死区域神经纤维密度以及基因表达谱进行检测分析。与MI组相比，MI+LLVNS组犬的室性心律失常发生率更低（p<0.05），左心室功能更优。LLVNS可显著抑制过度交感神经发芽，具体表现为酪氨酸羟化酶（tyrosine hydroxylase, TH）、生长相关蛋白43（growth-associated protein 43, GAP43）及神经丝蛋白（neurofilament, NF）阳性神经纤维密度显著降低（p<0.05）。基因表达谱分析显示，MI+LLVNS组与MI组犬间共鉴定出206个差异表达基因，主要涉及心脏组织重构、心脏神经重构、免疫应答及细胞凋亡过程。上述差异表达基因包含55个上调基因与151个下调基因，在LLVNS干预下呈现出更具保护性的表达模式。

结论：本犬类实验研究表明，LLVNS在实施过程中不会改变心率，可降低室性心律失常发生率并改善左心室功能。其潜在作用机制包括通过调控基因表达，抑制心脏神经发芽与过度交感神经发芽，同时减轻促炎反应。