Stellate Ganglionectomy Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

Abstract

Background: Enhanced cardiac sympathetic activity contributes to chronic heart failure (CHF). Interventions targeting the stellate ganglion (SG) can reduce this activity, potentially slowing the progression of cardiovascular diseases. This study examined the effects and mechanisms of stellate ganglionectomy on myocardial hypertrophy and cardiac dysfunction caused by pressure overload.

Methods: A rat model of pressure overload was created using abdominal aortic constriction. Four groups were studied: the sham surgery, abdominal aortic coarctation (AB), aortic constriction plus left stellate ganglionectomy (LSG), and aortic constriction plus right stellate ganglionectomy (RSG) groups. Cardiac function was assessed via echocardiography, and myocardial hypertrophy and fibrosis were evaluated using hematoxylin-eosin staining (H&E) and Masson staining. Serum atrial natriuretic peptides (ANP) and norepinephrine (NE) levels were measured using enzyme linked immunosorbent assay (ELISA), and the levels of the molecular markers tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP43) were analyzed using Western blotting and PCR. Calcium calmodulin dependent protein kinase II (CaMKII) and phosphorylated Ryanodine Receptor 2 (p-RyR2) expression were also investigated.

Results: Stellate ganglionectomy significantly reduced myocardial hypertrophy and improved cardiac function, as indicated by decreased left ventricular posterior wall thickness (LVPWD) (p < 0.01), left ventricular end-diastolic diameter (LVEDD) and volume (p < 0.001), left ventricular end-diastolic volume (LVEDV) (p < 0.001), increased left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular fractional shortening (LVFS) (p < 0.001). Histological analysis confirmed reduced myocardial dilation. Molecular analysis revealed decreased CaMKII/RyR2 signaling (p < 0.001) and lower NE levels (p < 0.01), suggesting reduced neurohormonal stress.

Conclusions: Stellate ganglionectomy alleviates hypertrophy and cardiac dysfunction caused by pressure overload, likely through inhibition of the CaMKII/RyR2 pathway, underscoring its potential as a therapeutic approach.