Selective ablation of the ligament of Marshall reduces ischemia and reperfusion-induced ventricular arrhythmias.

Ruisong Ma,Da Luo,Xiaomei Yu,Zhiliang Qin,Huihui Hu,Shan Liu,Hong Jiang,Weiyi Qu,Zhibing Lu,John Calvert

doi:10.1371/journal.pone.0203083

Abstract

Cardiac sympathetic tone overdrive is a key mechanism of arrhythmia. Cardiac sympathetic nerves denervation, such as LSG ablation or renal sympathetic denervation, suppressed both the prevalence of VAs and the incidence of SCD. Accumulating evidence demonstrates the ligament of Marshall (LOM) is a key component of the sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study aimed to investigate the roles of the distal segment of LOM (LOMLSPV) denervation in ischemia and reperfusion (IR)-induced VAs, and compared that LSG denervation. Thirty-three canines were randomly divided into group 1 (IR group, n = 11), group 2 (LOMLSPV Denervation + IR, n = 9), and group 3 (LSG Denervation + IR, n = 13). Hematoxylin-Eosin (HE) and Immunohistochemistry staining revealed that LOMLSPV contained bundles of sympathetic but not parasympathetic nerves. IR increased the cardiac sympathetic tone [serum concentrations of noradrenaline (NE) and epinephrine (E)] and induced the prevalence of VAs [ventricular premature beat (VPB), salvo of VPB, ventricular tachycardia (VT), VT duration (VTD) and ventricular fibrillation (VF)]. Both LOMLSPV denervation and LSG denervation could reduce the cardiac sympathetic tone in Baseline (BS) [heart rate variability (HRV)]. Compared with group 1, LOMLSPV denervation and LSG denervation similarly reduced sympathetic tone [NE (1.39±0.068 ng/ml in group 2, 1.29±0.081 ng/ml in group 3 vs 2.32±0.17 ng/ml in group 1, P<0.05) and E (114.64±9.22 pg/ml in group 2, 112.60±9.69 pg/ml in group 3 vs 166.18±15.78 pg/ml in group 1, P<0.05),] and VAs [VT (0±3.00 in group 2, 0±1.75 in group 3 vs 8.00±11.00 in group 1, P<0.05) and VTD (0 ± 4 s in group 2, 0±0.88s in group 3 vs 10.0 ± 22.00s in group 1, P<0.05)] after 2h reperfusion. These findings indicated LOMLSPV denervation reduced the prevalence of VT by suppressing SNS activity. These effects are comparable to those of LSG denervation. In myocardial IR, the anti-arrhythmic effects of LOMLSPV Denervation may be related to the inhibition of the expression of NE and E.

Highlights

Reperfusion therapies are the most effective therapies for myocardial infarct
Samples obtained from the LOMLSPV of animals in group 1 and group 3 contained bundles of fibers (Fig 3A) that consisted of an abundance of sympathetic (Fig 3B) but not parasympathetic (Fig 3C) nerves
We further demonstrate that left stellate ganglion (LSG) denervation markedly reduced the prevalences of ventricular tachycardia (VT) and VT duration (VTD) in a canine myocardial ischemia and reperfusion (IR) model by suppressing cardiac sympathetic nervous activity (LF/HF, NE and E)

Summary

Introduction

Reperfusion therapies are the most effective therapies for myocardial infarct. In addition to its beneficial effects, reperfusion causes kinds of injuries, including ventricular arrhythmias (VAs) or even lethal ones. Autonomic nervous imbalance manifesting with over-activated sympathetic drive and withdrawn vagal tone was markedly associated with adverse cardiac events in a model of myocardial ischemia [1]. The activation of the cardiac sympathetic nervous system (SNS), especially the left stellate ganglion (LSG), worsens the prevalence of VAs and sudden cardiac death (SCD) [2]. Cardiac SNS denervation, such as LSG ablation or renal sympathetic denervation, suppressed both the prevalence of VAs and the incidence of SCD [3,4,5]

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Results

Conclusion