Effects Of Catheter-based Renal Sympathetic Denervation On Ventricular Remodeling And Sympathetic Neural Remodeling After Acute Myocardial Infarction In Dogs

Objective:Excessive sympathetic activation not only leads to ventricular remodeling but also induces sympathetic neural remodeling after acute myocardial infarction.The aim of the study was to investigate the therapeutic and protective effects of catheter-based renal sympathetic denervation (RSD) on post-myocardial infarction (MI) cardiac remodeling and sympathetic neural remodeling in dogs, and explore the most optimal time for intervention.Methods:Thirty mongrel dogs were randomly assigned to RD group:including RD1w+MI group(RD1week before MI,n=6), MI1w+RD group (RD1week after MI, n=6), MI2w+RD group (RD2weeks after MI, n=6),Normal group (n=6) and MI group(n=6).Establishing a craine model of acute myocardial infarction by interventional occlusion with gelatin sponge via femoral artery, RD group of dogs received Renal Sympathetic Denervation(RSD)1week before and1week,2weeks after myocardial infarction. And Blood samples were taken at baseline and4weeks after embolization, detection of brain natriuretic peptide (BNP) and endothelin-1(ET-1) levels. At the same time, echocardiography was performed to know cardiac function and heart size. Sacrificed all the dogs at end of experiment and the samples of cardiac and renal arteries was obtained. The expression of MMP-2, MMP-9, TH in the cardic and renal arteries were got by immunohistochemistry, Western blot determined the protein expression of TH,GAP43in peri-MI zone, Real Time-PCR detected the mRNA expression of NGF.Results:1. In MI group, the level of BNP, ET-1increased significantly compared with N group (p<0.05),LVEF,LVPWd,IVSd decresed significantly,LVEDd increased significantly compared with N group(all p<0.05), the expression of MMP-2and MMP-9increased significantly compared with N group(p<0.05), and the protein expression of TH and GAP43,and the gene expression of NGF in peri-MI zone was higher than that in N group(p<0.05).2. Heart rate of RD group was lower than MI group (p<0.05), but was not statistically significant compared with the normal group(p>0.05); The distribution of sympathetic nerve in reanl artery was reduced after renal sympathetic denervation (p<0.05).3.In RD group(including RDlw+MI group,MI1w+RD group,MI2w+RD group),the level of BNP,ET-1decreased significantly campared with MI group(p<0.05), but higher than the N group(p<0.05), no significantly difference among the RDlw+MI group,MIlw+RD group,MI2w+RD group.4.In RD group(including RDlw+MI group,MIlw+RD group,MI2w+RD group),the LVEF, LVPWd was significantly higher than that in MI group(p<0.05),and LVEDd was reduced significantly than MI group (p<0.05), IVSd in RD1w+MI and MI1w+RD group was significantly higher campared with MI group,but IVSd in MI2w+RD group has no difference with MI group(p>0.05);However, the LVEF, IVSd, LVPWd was significantly lower than that in N group (p<0.05), and LVEDd was increased significantly compared with N group (p<0.05).5.The expression of myocardial MMP-2,MMP-9in RD group was significantly lower than that in MI group (p<0.05),and higher than that in N group (p<0.05).but no significantly difference among the RDlw+MI group,MIlw+RD group,MI2w+RD group(all p>0.05).6.The protein expression of myocardial TH and GAP43in RD group was signicantly lower than that in MI group (p<0.05),higher than the nomal group (p<0.05).In addition, protein expression of GAP43in RD1w+MI group and MI1w+RD lower than MI2w+RD group(both p<0.05).The gene expression of myocardial NGF in MI+RD group was signicantly lower than that in MI group (p<0.05),higher than the N group (p<0.05).In addition,gene expression of NGF in RD1w+MI group and MI1w+RD lower than MI2w+RD group(both p<0.05).Conclusion:1. The craine model of post-MI ventricular remodeling and sympathetic neural remodeling was built successfully and reliablely.2. Renal sympathetic denervation decreased HR significantly; decreased the distribution of TH positive nerve fiber in renal artery.3. Renal sympathetic denervation reduced the level of BNP and ET-1 significantly.4. Renal sympathetic denervation improved cardiac function and the size of cardiac.5. Renal sympathetic denervation improved post-myocardial infarction myocardial interstitial remodeling by down-regulating the expression of MMP-2and MMP-9.6. Renal sympathetic denervation. improves post-myocardial infarction sympathetic neural remodeling in peri-MI zone by down-regulation the expression of NGF mRNA, TH and GAP43.