Effect of bilateral sympathectomy in a rat model of dilated cardiomyopathy induced by doxorubicin

J Thorac Cardiovasc Surg. 2020 Sep;160(3):e135-e144. doi: 10.1016/j.jtcvs.2019.09.031. Epub 2019 Sep 26.

Abstract

Objective: The study objective was to evaluate the effect of bilateral sympathectomy on ventricular remodeling and function in a rat model of dilated cardiomyopathy induced by doxorubicin.

Methods: Dilated cardiomyopathy was induced in male Wistar rats by weekly intraperitoneal injection of doxorubicin (2 mg/kg) for 9 weeks. Animals were divided into 4 groups: dilated cardiomyopathy; bilateral sympathectomy, submitted on day 15 of the protocol to bilateral sympathectomy; angiotensin-converting enzyme inhibitor, treated with enalapril through day 15 until the end of the experimental protocol; and sham, nonsubmitted through doxorubicin protocol, with weekly intraperitoneal injections of saline solution (0.9%). The left ventricular function was assessed, and the heart was collected for posterior analyses.

Results: The dilated cardiomyopathy group presented a significant decrease in the myocardial efficiency when compared with the sham group (33.4% vs 71.2%). Only the bilateral sympathectomy group was able to preserve it (57.5%; P = .0001). A significant dilatation in the left ventricular chamber was observed in the dilated cardiomyopathy group (15.9 μm2) compared with the sham group (10.2 μm2; P = .0053). Sympathectomy and enalapril prevented ventricular remodeling (9.5 and 9.6 μm2, respectively; P = .0034). There was a significant increase in interstitial myocardial fibrosis in the dilated cardiomyopathy group (14.8%) when compared with the sham group (2.4%; P = .0001). This process was significantly reduced with sympathectomy and enalapril (8.7 and 3.9%, respectively; P = .0001).

Conclusions: Bilateral sympathectomy was effective in preventing remodeling and left ventricular dysfunction in a rat model of dilated cardiomyopathy induced by doxorubicin.

Keywords: apoptosis; dilated cardiomyopathy; doxorubicin; left ventricular function; left ventricular remodeling; sympathectomy.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Cardiomyopathy, Dilated / chemically induced*
  • Cardiomyopathy, Dilated / surgery*
  • Disease Models, Animal
  • Doxorubicin / toxicity*
  • Enalapril / administration & dosage
  • Humans
  • Male
  • Rats
  • Rats, Wistar
  • Sympathectomy*
  • Ventricular Dysfunction, Left / prevention & control
  • Ventricular Remodeling

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Enalapril
  • Doxorubicin