The Role Of Endothelin-1 In Ventricular Arrhythmia After Acute Myocardial Infarction And The Underlying Neurological Mechanism

Objectives To investigate the effect of endothelin-1(ET-1)on ventricular arrhythmia after acute myocardial infarction and its neural mechanism,and further explore whether the mechanism of endothelin-1 regulation of nerve involves PI3K/Akt/GSK-3β signaling pathway and inflammatory response.Methods Twelve male adult beagle dogs were randomly divided into two groups,six beagles in each group: Control group(local microinjection of normal saline,ligation at the lower edge of the first diagonal branch of the left anterior descending coronary artery,induced acute myocardial infarction)and ET-1 group(local microinjection of ET-1 after ligation at the same site,induced acute myocardial infarction).The function,activity,and effective refractory period(ERP)of the left stellate ganglion(LSG)were measured at baseline and 30 min after microinjection.Arrhythmia events within 60 minutes after acute myocardial infarction were continuously recorded using an electrophysiological recorder.Western blotting was used to detect the expression levels of P-PI3 K,PI3K,AKT2,GSK3β and P-GSK3β;Real-time quantitative fluorescent PCR was used to detect the levels of IL-1β,IL-6 and TNF-α;HE staining was used to observe the histopathology of LSG of Beagle dogs;immunofluorescence staining to observe the expression of endothe lin receptor,NGF,c-fos and TH in LSG tissues.Results Compared with the Control group,ET-1 local microinjection significantly reduced ventricular ERP,increased ventricular electrophysiological instability,and increased the incidence of ventricular arr hythmia after acute myocardial infarction.At the same time,local microinjection of ET-1 increased the function and activity of LSG in normal and acute myocardial infarction(AMI)hearts.In addition,local microinjection of ET-1 significantly increased the expression levels of proinflammatory cytokines,c-fos and NGF in LSG compared to the Control group.what’s more,this study further validated the presence of endothelin A receptors in LSG,and its downstream PI3K/Akt/GSK-3β signaling pathway was significantly activated by ET-1.Conclusions LSG activation induced by local microinjection of ET-1 may aggravate ventricular arrhythmias induced by acute myocardial infarction.The mechanism by which ET-1 induces LSG activation may involve activation of endothelin type A receptors and downstream signaling pathways and upregulation of proinflammatory cytokine levels in LSG.