Effects Of Renal Denervati On Cardiac Oxidative Stress And Ventricular Remodeling After Myocardial Infaction In Canine

Background Acute myocardial infarction(AMI) is one of the most serious diseases that threat human health. Chronic heart failure(CHF) is a major complication post-myocardial infarction(MI) in the surviving patients. Studies have shown that ventricular remodeling is the important pathogenetic basis of CHF. Ventricular remodeling is a complex pathophysiological process, and sympathetic nervous system plays an important role in this process. Oxidative stress is one of the crucial initiating factors resulting in the development and progression of CHF. Renal denervation(RDN) is available as a new strategy for the treatment of resistant hypertension, and has shown to be effective in conditions with enhanced sympathetic activity like left ventricular hypertrophy, ventricular tachycardia and sleep apnea.Objective To observe the effects of RDN on the cardiac Oxidative Stress and ventricular remodeling due to MI in canine.Methods Anterior myocardial infarction was produced by gelatin sponge embolization of the left anterior descending artery. Eighteen canine were randomly divided into three groups. SHAM group(Sham operation group, renal arteriography performed a week after coronary angiograph, n=6), MI group(renal arteriography performed a week after MI, n=6), RDN group(RDN performed a week after MI, n=6). Four weeks post-MI, echocardiography examination was administered to identify left ventricular end-diastolic dimension(LVEDD), left ventricular end-systolic dimension(LVESD), fraction shortening(FS) and left ventricular ejection fraction(LVEF). Left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and heart rate(HR) were measured. Myocardial superoxide dismutase(SOD) activity, malondialdehyde(MDA), anti-superoxide anion free radical(ASAFR) activity and expression of p47 phox m RNA were detected. Immunohistochemical assay was used to analyze the distribution and density of tyrosine hydroxylase(TH) positive staining nerve fibers in kidney. Serum creatinine was detected 4 weeks post-MI to assess renal function.Results Compared with SHAM group, LVEF, FS and LVSP were decreased in MI group and RDN(P<0.05), but LVEDD、LVESD and LVEDP were increased(P<0.05). In contract, compared with MI group, LVEF was increased(P=0.028), while LVEDD and LVESD were significantly lowered in RDN group(P<0.05), but no significant differences were observed in FS and LVSP between the two groups(P=0.092/0.931). There were no significant differences in heart rate among the three groups(P=0.621).Although the levels of SOD lower and ASAFR activity, MDA and p47 phox m RNA were higher in MI group and RDN group, compared to the SHAM group(P<0.05), they were all significantly improved in RDN group compared to the MI group(P<0.05). Between-group comparisons demonstrated no differences in serum creatinine(P=0.706).Conclusions RDN should have effects to decrease the level of cardiac oxidative stress, attenuate cardiac remodeling, improve heart function and decrease renal sympathetic nerve activity without affecting renal function in post-MI HF canine model.