Interaction between Endothelin-1 and Left Stellate Ganglion Activation: A Potential Mechanism of Malignant Ventricular Arrhythmia during Myocardial Ischemia

Abstract

Endothelin-1 (ET-1) is synthesized primarily by endothelial cells. ET-1 administration in vivo enhances the cardiac sympathetic afferent reflex and sympathetic activity. Previous studies have shown that sympathetic hyperactivity promotes malignant ventricular arrhythmia (VA). The aim of this study was to investigate whether ET-1 could activate the left stellate ganglion (LSG) and promote malignant VA. Twelve male beagle dogs who received local microinjections of saline (control, n=6) and ET-1 into the LSG (n=6) were included. The ventricular effective refractory period (ERP), LSG function, and LSG activity were measured at different time points. VA was continuously recorded for 1 h after left anterior descending occlusion (LADO), and LSG tissues were then collected for molecular detection. Compared to that of the control group, local ET-1 microinjection significantly decreased the ERP and increased the occurrence of VA. In addition, local microinjection of ET-1 increased the function and activity of the LSG in the normal and ischemic hearts. The expression levels of proinflammatory cytokines and the protein expression of c-fos and nerve growth factor (NGF) in the LSG were also increased. More importantly, endothelin A receptor (ETA-R) expression was found in the LSG, and its signaling was significantly activated in the ET-1 group. LSG activation induced by local ET-1 microinjection aggravates LADO-induced VA. Activated ETA-R signaling and the upregulation of proinflammatory cytokines in the LSG may be responsible for these effects.

Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis

“…Nerve growth factor is a key cytokine thought to promote autonomic nerve sprouting in the ventricle 96,113,114 and atrium, 113,115,116 and its production in target organs determines the density of innervation by the sympathetic nervous system. 96,117 Cardiac sympathetic left stellate ganglion (LSG) activity increases markedly before VA onset in an ischemia model, 118 and the inhibition of LSG activity effectively reduces the incidence of VA. [118][119][120][121] Accordingly, it was recently reported that non-invasive light-emitting diode therapy might significantly reduce both sympathetic activation, manifested by a decrease in LSG neural activity and expression of NGF, and inflammatory response in the myocardium, thus reducing the incidence of acute MI-induced VAs. 121 Cao et al 122 demonstrated that heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation play important roles in arrhythmogenesis and SCD in both human patients and the animal models of MI.…”

Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis

“…The stellate ganglion comprises the sixth and seventh cervical vertebrae as well as the first thoracic sympathetic ganglion, functionally belonging to the sympathetic nerve. When stimulated by inflammation and serious pressure, the body will experience imbalances between the sympathetic nerve and the parasympathetic nerve, which then elicits diseases concerning sympathetic nerve regulation like arrhythmia [ 4 , 5 ]. SGB blocks the sympathetic nerve and redresses the vegetative nerve imbalance through the injection of anesthetic drugs into stellate ganglion tissues, thus meeting its goal of stabilizing the internal environment of the body [ 6 ].…”

Classic and Novel Biomarkers as Potential Predictors of Ventricular Arrhythmias and Sudden Cardiac Death

“…Several mechanisms are proposed to be activated via ET1 to promote arrhythmic events. Nevertheless, early afterdepolarizations triggered by ion channel remodeling, but also sympathetic activation, were suggested to be the main causes of ET1 induced arrhythmias [133][134][135]. Inspired by these promising results, further research focused on patients with decompensated HF.…”