Adult: Coronary: Basic Science
Effect of bilateral sympathectomy in a rat model of dilated cardiomyopathy induced by doxorubicin

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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.

Graphical abstract

After a cardiac insult and myocardium overload, the sympathetic nervous system activity increases as a compensatory mechanism. However, this mechanism leads to further decompensation with ventricular remodeling observed by an enlarged left ventricle, myocardial extracellular fibrosis, increased apoptosis, and subsequent loss of function. With sympathetic blockade, LV remodeling was prevented and cardiac function was preserved.

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Key Words

sympathectomy
dilated cardiomyopathy
doxorubicin
left ventricular remodeling
left ventricular function
apoptosis

Abbreviations and Acronyms

ACEI
angiotensin-converting enzyme inhibitor
BS
bilateral sympathectomy
DBT
dobutamine
DCM
dilated cardiomyopathy
HR
heart rate
ICAM
intercellular adhesion cellular molecule
LS
left sympathectomy
LV
left ventricular
LVEF
left ventricular ejection fraction
LVSW
left ventricular stroke work
MMP
matrix metalloproteinase
PRSW
preload recruitable stroke work
TBST
tris-buffered saline Tween-20
VEGF
vascular endothelial growth factor

Cited by (0)

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES)–Finance Code 001.