Abstract
BackgroundThis study assessed the therapeutic effects of renal sympathetic denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and sympathetic neural remodeling in dogs. The possible mechanisms and optimal time for treatment are discussed.MethodsWe randomly assigned 30 dogs to five groups: RDN 1 week before MI (RDN1w + MI; n = 6), RDN 1 week after MI (MI1w + RDN; n = 6), RDN 2 weeks after MI (MI2w + RDN; n = 6), control (N; n = 6), and MI (n = 6). A canine model of myocardial infarction was established by interventional occlusion with a gelatin sponge via the femoral artery. Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels were measured and echocardiography was performed to assess cardiac function and heart size. All dogs were killed at the end of the experiment and samples of cardiac and renal arteries were obtained. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 in cardiac and of tyrosine hydroxylase (TH) in renal arteries was assessed by immunohistochemistry. Sympathetic innervations in the infarction border zone were investigated via Western blotting and real-time PCR.ResultsLeft ventricular function in the MI group decreased significantly, while plasma BNP and ET-1 levels as well as MMP-2 and MMP-9 expression increased. Compared with the MI group, the RD groups showed significantly reduced MMP‑2, MMP‑9, TH, and growth-associated protein (GAP) 43 expression in the RDN1w + MI, MI1w + RDN, and MI2w + RDN groups was significantly improved. Additionally, the expression of TH in renal arteries decreased after RDN.ConclusionRDN has preventive and therapeutic effects on post-MI ventricular remodeling and sympathetic neural remodeling. The mechanism of RDN is likely mediated through restraint of renal sympathetic nerve activity.
Highlights
This study assessed the therapeutic effects of renal sympathetic denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and sympathetic neural remodeling in dogs
In the MI group, two dogs died 1 day after acute MI (AMI) because of arrhythmias, and one dog died of heart failure 3 weeks after AMI
Through immunohistochemical staining and by calculating the immunohistochemical score (IHS), we found the expression of matrix metalloproteinase (MMP)-2 and matrix metalloproteinase-9 (MMP-9) in the left ventricle (LV) to be significantly reduced in the RDN1w + MI, MI1w + RDN, and MI2w + RDN groups compared with the MI group, and to be significantly increased compared with the N group
Summary
Experiments were carried out using 30 mongrel dogs weighing 15–20 kg, which were purchased through the Experimental Animal Care Center of Tianjin Medical University. The catheter was subsequently withdrawn by 1–2 cm, circumferentially rotated, and a further dose of RF energy was applied This procedure was repeated four to six times in the in-. Immunohistochemical staining was performed using the Power VisionTM twostep method. The sections were incubated overnight at 4°C with primary antibody and with horseradish peroxidase-conjugated second antibody (Santa Cruz, CA, USA). We utilized an immunohistochemical score (IHS), which is based on the German ImmunoReactive score; this method has been shown to approximate data generated from image analysis-based scoring systems, as in a previous study [2]. The expression levels of candidate genes were measured by real-time quantitative RT-PCR using an SYBR Green PCR Master mix In each assay, both glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the nerve growth factor (NGF) gene from the same samples were amplified in triplicate in separate tubes.
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