Cardiac Dysregulation and Myocardial Injury in a 6-Hydroxydopamine-Induced Rat Model of Sympathetic Denervation

PLoS One. 2015 Jul 31;10(7):e0133971. doi: 10.1371/journal.pone.0133971. eCollection 2015.

Abstract

Background: Cardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated.

Methods: Twenty-four rats were assigned to the normal control group (NC), sympathectomy control group (SC), and a sympathectomy plus mecobalamin group (SM). Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV) myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV), ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction.

Results: Injection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01) and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01) concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group.

Conclusions: Chemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / analysis
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Heart / drug effects
  • Heart / innervation
  • Heart / physiopathology*
  • Heart Injuries / physiopathology*
  • Heart Ventricles / chemistry
  • Heart Ventricles / innervation
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Male
  • Microscopy, Electron, Transmission
  • Oxidopamine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sympathectomy* / adverse effects
  • Vagus Nerve / drug effects

Substances

  • Cytokines
  • Oxidopamine

Grant support

This work was funded by Chinese national natural science foundation #81072962 and Shan Dong Province “Taishan Scholar” Construction Project Awards #2012-55.