Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction

PLoS One. 2017 Jul 21;12(7):e0181322. doi: 10.1371/journal.pone.0181322. eCollection 2017.

Abstract

Background: Modulation of the autonomic nervous system (ANS) has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.

Methods: Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT) and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.

Results: Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05). Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05). The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05). However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV), left atrial diameter (LA), ejection fraction (EF).

Conclusions: Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Dogs
  • Electric Stimulation
  • Female
  • Heart / innervation*
  • Immunohistochemistry
  • Male
  • Muscle Denervation*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • Myocardium / pathology
  • Neurons / pathology
  • Neurons / physiology
  • Random Allocation
  • Stellate Ganglion / pathology
  • Stellate Ganglion / physiopathology
  • Sympathectomy*
  • Ventricular Fibrillation / pathology
  • Ventricular Fibrillation / physiopathology
  • Ventricular Fibrillation / surgery*

Grants and funding

This work was supported by Scientific Research Projects of Heilongjiang Province, Award Number 201403 (Recipient: Jingjie Li); and Scientific Research Projects of Heilongjiang Province, Award Number: 201607 (Recipient: Jingjie Li). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.