title: Cardioprotective effects of low-level carotid baroreceptor stimulation against myocardial ischemia-reperfusion injury in canine model.
abstract: OBJECTIVE
  The modulation of the autonomic nervous system (ANS) has been shown to prevent myocardial ischemia-reperfusion injury (MIRI). Carotid baroreceptor stimulation modulates the ANS by sympathetic withdrawal and vagal activation. The aim of this study was to assess whether low-level carotid baroreceptor stimulation (LL-CBS) attenuated MIRI and test its underlying molecular mechanisms.
  
  
  METHODS
  Forty adult healthy mongrel dogs were randomly assigned to three groups as follows: (1) I/R group (n = 15): left anterior descending artery (LAD) was occluded for 1 h and allowed for 1 h reperfusion; (2) LL-CBS group (n = 15): I/R plus LL-CBS; and (3) sham group (n = 10): sham surgery without stimulation. The voltage-reducing blood pressure by 5% was defined as the threshold. LL-CBS was performed at a voltage that is 80% below the threshold. Infarct size was assessed with Evans blue and TTC staining. The inflammatory cytokines, biomarker of oxidative stress and apoptosis, and connexin 43 (Cx43) expression were measured to assess the injury.
  
  
  RESULTS
  The number of ventricular tachycardia/ventricular fibrillation (VT/VF) episodes was significantly decreased in the LL-CBS group compared with the I/R group (2.8 ± 0.8 vs. 7.0 ± 2.6, P < 0.05). LL-CBS reduced tumor necrosis factor α, interleukin (IL)-1, IL-6, and malondialdehyde levels but increased superoxide dismutase level compared with the I/R group (P < 0.05). Meanwhile, LL-CBS significantly decreased the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL)-positive cardiomyocytes (20 ± 8 vs. 47 ± 12, P < 0.05). Western blotting and real-time polymerase chain reaction (RT-PCR) in Cx43 revealed that LL-CBS caused an increase, respectively, compared with the I/R group (0.75 ± 0.3 vs. 0.3 ± 0.2 and 1.0 ± 0.3 vs. 0.4 ± 0.1, respectively, both P < 0.05).
  
  
  CONCLUSIONS
  LL-CBS exerted cardioprotective effects during ischemic reperfusion period potentially by inhibiting inflammation, oxidative stress, and apoptosis and modulating the Cx43 expression.
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, Hangzhou City, Zhejiang Province, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province, People's Republic of China.
authors.forename: Mingxian
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province, 430060, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Cardiology, First Hospital of Jilin University, No. 71 Xinmin street, Changchun city, Jilin province, 130021, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province, 430060, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province, 430060, People's Republic of China. mbao@whu.edu.cn.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Bao
authors.affiliation: Department of Cardiology, First Hospital of Jilin University, No. 71 Xinmin street, Changchun city, Jilin province, 130021, People's Republic of China. jilishuyan@163.com.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D017704:Baroreflex; D002339:Carotid Arteries / Q000503:physiopathology*; D004285:Dogs; D004599:Electric Stimulation Therapy / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000503:physiopathology* / Q000517:prevention & control*; D018384:Oxidative Stress; D011311:Pressoreceptors / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D017382:Reactive Oxygen Species
keywords: Autonomic nervous system; Carotid baroreceptor stimulation; Ischemia and reperfusion; Ventricular arrhythmia