Effects Of Stellate Ganglion Resection On Heart Failure In Response To Abdominal Aorta Constriction In Rats And Its Mechanism

Background: Cardiac autonomic nervous system imbalance,especially enhanced sympathetic nerve activity,is one of the pathophysiological characteristics of chronic heart failure(CHF).Autonomic nerve imbalance and hypersympathetic nerve activity lead to high activation of β-adrenergic receptors,leading to a series of pathophysiological changes,which have serious effects on cardiac structure and function,such as myocardial hypertrophy,myocardial fibrosis,myocardial apoptosis,left ventricular remodeling,arrhythmias,reduced cardiac function,heart failure,and even sudden death.The stellate ganglion(SG)is an important part of the heart’s external sympathetic nerves and is widely involved in cardiac innervation.Intervention of SG can inhibit the excitability of the sympathetic nerves that dominate the heart,and thus has inhibitory effects on a variety of cardiovascular diseases,such as hypertension,long QT syndrome,and arrhythmia.However,it has not been reported whether intervention of SG has an effect on heart failure.Obiectives:In this study,abdominal aorta constriction was performed in rats to induce a stress overload heart failure model,and the left and right stellate ganglia were resected separately to explore the effect of stellate ganglion resection on heart failure and its molecular mechanism.Methods:Forty male SD rats were randomly divided into 4 groups: abdominal aortic constriction group,that is,the AB group(n = 10),abdominal aortic constriction operation and left stellate ganglion(LSG)resection group,that is,LSG Group(n =10),abdominal aortic stenosis + right stellate ganglion(RSG)resection group,namely RSG group(n = 10),and another 10 were taken as control group(n = 10).Rats in the AB group,LSG group,and RSG group were induced by pressure aortic heart failure model through abdominal aortic constriction.After 30 minutes,the left and right stellate ganglia were removed by surgery in the LSG and RSG groups,respectively.Changes in blood pressure and heart rate of the abdominal aorta of the experimental rats before surgery,30 minutes after surgery,and 10 weeks after surgery were recorded.Rats were examined by echocardiography 10 weeks after feeding,and the end-ventricular septal thickness(IVSTd),Left ventricular posterior wall end-diastolic thickness(LVPWd)and left ventricular end-diastolic volume(LVEDV),and calculated left ventricular shortening rate(LVFS)and left ventricular ejection fraction(LVEF)to determine changes in left ventricular thickness and cardiac output function in rats;After the rats were sacrificed,specimens were taken,and the ratios of heart weight / body weight(HW / BW),lung weight / body weight(LW / BW)and heart weight / tibia length(HW / TL)were measured and cardiac changes were observed;serological examination To detect the level of brain natriuretic peptide(BNP)in serum to determine the degree of heart failure,to detect the level of norepinephrine(NE)in serum to determine the content of catecholamines in blood;pathological examination,myocardium Tissue HE staining and Masson staining were used to observe myocardial hypertrophy and myocardial fibrosis;Westernblot test was used to detect the relationship between tyrosine hydroxylase(TH)and growth in myocardial tissue White-43(growth associated protein 43,GAP43)expression levels to determine the regeneration of sympathetic nerve fibers in cardiac tissue,to detect calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ),ryanodine receptors 2 (Ryanodine Receptor2,Ry R2)and phosphorylated ryanodine receptor 2(p-RYR2) expression levels,and calculated the ratio of Ry R2 / p-RYR2,to determine the expression of Ca MKⅡ in myocardial tissue and the level of RYR2 phosphorylation.Results:Heart rate and blood pressure records show that 30 minutes after abdominal aortic constriction,the AB group,LSG group,and RSG group have significantly increased blood pressure and heart rate compared with before surgery;and the LSG group and RSG group have 30 minutes and The blood pressure at 10 weeks after operation was significantly lower than that of the AB group,and the heart rate was also significantly lower than that of the AB group.Echocardiographic examination showed that at 10 weeks after surgery,the AB,LSG,and RSG groups had significantly increased LVEDD and LVEDV,and LVEF and LVFS were significantly lower than those before surgery;compared with the AB group,the LSG and RSG groups LVEDD and LVEDV were significantly reduced,and LVEF and LVFS were significantly increased.Ten weeks after the operation,the rats were sacrificed and the specimens were sacrificed,and the ratios of HW / BW,LW / BW,and HW / TL were measured and calculated.Compared with the control group,the AB group increased significantly,and the LSG group decreased significantly compared to the AB group.In the trend,the HW / BW and HW / TL in the RSG group were significantly lower than those in the AB group.The results of pathological examination showed that compared with the AB group,the content of type I collagen fibers in the myocardium of the rats in the LSG group and the RSG group was significantly reduced,and the ratio of type I and type III collagen fibers was also significantly reduced.Serological tests showed that the expression levels of BNP and NE in the AB group were significantly increased compared to the control group,and the LSG and RSG groups were significantly decreased compared to the AB group.Westernblot showed that the ratios of TH,GAP43,Ca MKⅡ,and Ry R2 / p-RYR2 in myocardial tissue of the AB group were significantly higher than those in the control group.The LSG group had a significant downward trend compared to the AB group,and the RSG group had a TH,GAP43,and AB relative to the AB group.The expression of Ca MKⅡ decreased significantly.Conclusions:LSG resection can reduce myocardial hypertrophy,myocardial fibrosis,improve cardiac function,and delay the process of heart failure caused by stress overload.The underlying molecular mechanism may be related to the inhibition of Ca MKⅡ overexpression in cardiomyocytes by RYR2 hyperphosphorylation after LSG resection.Level-dependent,RSG resection has a similar effect.