Effect Of Renal Denervation On Cardiac Function And Apoptosis-related Genes’ Expression In Heart Failure Dogs

Background Cardiomyocyte apoptotsis is one of the important pathogenesis of myocardial infarction-induced heart failure(MI-HF)and is involved in the development process of HF.The local adverse stimulus after MI induces cell apoptosis,promotes the deterioration of cardiac function and ventricular remodeling.The loss of myocardial cells is associated with impaired heart function,thus inhibiting the adverse stimulus after MI to lower the myocytes apoptosis,reduce cardiac remodeling and improve heart function has an important clinical significance for the heart failure’s treatment.Renal denervation(RDN)has become a hot spot in the field of HF treatment.Previous animal studies have shown that RDN could improve the heart function by reducing cardiomyocyte apoptotsis caused by rapid ventricular pacing-induced atrial fibrillation.Whether RDN could regulate apoptosis in MI-HF and its mechanism is unclear.Objective To observe the effects of RDN on cardiac function and apoptosis-related genes’ expression in MI-HF dogs.Methods Eighteen healthy mongrel dogs were randomly divided into normal group(n=6),model group(n=6)and treatment group(n=6).MI-HF was established in model group and treatment group by anhydrous alcohol embolization,after heart failure model was established dogs in the treatment group and model group proceeded bilateral renal artery ablation and bilateral renal arteriography,respectively.The cardiac function parameters were measured;the serum NT-Pro BNP level was detected by ELISA;the degree of myocardial fibrosis was observed through masson staining;TUNEL method was used to observe cardiomyocyte apoptotsis and calculate the apoptosis index(AI).Relative expression of Bcl-2,Bax,Caspase-3 and GRP78 were detected using RT-PCR and WB.Renal artery HE staining and serum creatinine were conducted to access the the efficacy and safety of RDN.Results1,No statistical differences between the baseline weight,HR,LVEDD,LVESD,LVEF,LVEDP and LVSP in all dogs.Before ablation,compared with normal group,LVEDD,LVESD,LVEDP increased and LVEF,LVSP reduced in HF dogs(treatmentgroup and model group),while these parameters have no statistical differences between treatment group and model group.No difference was observed between HR in each group.4 weeks after ablation,compared with model group,the LVEDD,LVESD,LVEDP decreased and LVEF,LVSP increased in RDN treatment group,while compared with normal dogs the index of LVEDD,LVESD,LVEDP higher and LVEF lower in treatment group and model group.No difference was found between LVSP in normal group and treatment group.The LVSP decreased in model group when compared with normal group.HR in there groups had no statistical difference.2,Baseline NT-Pro BNP level had no statistical differences in all dogs.Before ablation,NT-Pro BNP level increased in HF dogs(treatment group and model group)compared with normal dogs,while no difference between treatment group and model group.4 weeks after ablation,compared with model group the NT-Pro BNP values reduced in treatment group.NT-Pro BNP level were higher in HF dogs.3,4 weeks after ablation,compared with normal group the Bax,Caspase-3,GRP78 m RNA and protein level in myocardial tissue have increased,Bcl-2 m RNA and protein expression decreased and cardiomyocyte apoptotsis index increased in heart failure HF dogs(model group and treatment group)with statistical significance;Compared with model group,the level of Bax,Caspase-3,GRP78 decreased,Bcl-2m RNA and protein expression increased,myocardial apoptosis index decreased in RDN treatment dogs with statistical significance.4,4 weeks after ablation,HE staining showed that the sympathetic nerve distribution decreased significantly after RDN operation.5,4 weeks after ablation,compared with normal group,serum creatinine values rised in dogs of model group,while the change of serum creatinine has no statistical significance in treatment dogs.Conclusion RDN could improve cardiac function in MI-HF dogs,and we speculate that its mechanism may be related to the raise of Bcl-2 gene expression and lower of Bax,Caspase-3,GRP78 expression level by RDN.