title: Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.
abstract: BACKGROUND
  This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action.
  
  
  METHODS
  Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47phoxmRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively.
  
  
  RESULTS
  We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47phox,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1-7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706).
  
  
  CONCLUSIONS
  RDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.
authors.affiliation: First Center Clinic College of Tianjin Medical University, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, Tianjin, 300192, China. lucz8@126.com.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, Tianjin, 300192, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Digestion, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Cardiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, Tianjin, 300192, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: First Center Clinic College of Tianjin Medical University, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Ravi Chandra
authors.initials: RC
authors.lastname: Uppada
mesh_terms: D000818:Animals; D017763:Autonomic Denervation; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D007668:Kidney / Q000294:innervation*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D020127:Recovery of Function; D012084:Renin-Angiotensin System; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers
keywords: Acute myocardial infarction; Oxidative stress; Renal denervation; Renin-angiotensin system; Sympathetic nervous system