Blocking the Nav1.8 channel in the left stellate ganglion suppresses ventricular arrhythmia induced by acute ischemia in a canine model

Figures

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  Figure 1. The LSG location (A), schematic representation of electrodes position in the left ventricular free walls (B) and the experimental design flowchart were shown (C). LSG = left stellate ganglion; LAA = left atrial appendage; LA = left atria; PA = pulmonary artery; LSPV = left superior pulmonary vein; LIPV = left inferior pulmonary vein; LV = left ventricular; LVA = left ventricular apex; LVB = left ventricular base; LVM = median area between LVA and LVB; DMSO = dimethylsulfoxide; APD = action potential duration; ERP = effective refractory period; LAD = left anterior descending coronary artery; VA = ventricular arrhythmia.

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  Figure 2. Effects of Nav1.8 channel block on the ventricular APD80 (A–C) and ERP (D–F). Blocking Nav1.8 channel with A-803467 significantly prolonged ventricular APD80 and ERP, whereas no significantly change was found in the DMSO group. *p < 0.05 vs DMSO group at 30 min, #p < 0.05 vs 10 mM group at 30 min. The abbreviations were similar with Fig. 1.

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  Figure 3. Effects of Nav1.8 channel block on VA episodes. (A) Representative ECG examples. (B–E) Quantitative analysis of the number and duration of different types of VA. *p < 0.05 vs DMSO group, #p < 0.05 vs 10 mM group. VA = ventricular arrhythmia; VPB = ventricular premature beat; VT = ventricular tachycardia; VF = ventricular fibrillation.

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  Figure 4. Effects of Nav1.8 channel block on LSG function. (A) The representative BP elevation example in response to LSG electrical stimulation. (B) The voltage/BP response curve in different groups. Blocking Nav1.8 channel attenuated LSG function. *p < 0.05 vs DMSO group, #p < 0.05 vs 10 mM group. SBP = systolic blood pressure.

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  Figure 5. Effect of Nav1.8 channel block on the mRNA expression of NGF (A) and c-fos (B) in LSG. NGF = nerve growth factor. *p < 0.05 vs DMSO group, #p < 0.05 vs 10 mM group.

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  Figure 6. Effect of Nav1.8 channel block on apoptosis of sympathetic neurons in LSG. (A) Representative images showing double-immunofluorescence staining for TH (red) and TUNEL (green) in LSG from DMSO group and 20 mM A-803467 group. (B) Quantification of the sympathetic neuron apoptosis (n = 3, *p < 0.05 vs DMSO group, #p < 0.05 vs 10 mM group). TH = Tyrosine hydroxylase.

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  Figure 7. Schematic diagram depicting the potential role of Nav1.8 channel in LSG and VA. LSG hyperactivity contributes to the VA under acute ischemia stress. Whereas, blocking Nav1.8 channel with its specific blocker A-803467 could inhibit LSG activity through decreased NGF expression and increased sympathetic neuron apoptosis, which subsequently attenuates ischemia induced VA.