title: Low-Level Vagus Nerve Stimulation Attenuates Myocardial Ischemic Reperfusion Injury by Antioxidative Stress and Antiapoptosis Reactions in Canines.
abstract: BACKGROUND
  Low-level vagus nerve stimulation (LL-VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion (I/R) injury. However, the underlying mechanism of this protective effect remains unknown.
  
  
  OBJECTIVE
  This study aimed to test the hypothesis that LL-VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions.
  
  
  METHODS
  Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL-VNS group (N = 9, I/R plus LL-VNS), and sham group (N = 9, sham surgery without LL-VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis.
  
  
  RESULTS
  LL-VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL-VNS in the I/R group induced the opposite effect compared with the sham group.
  
  
  CONCLUSIONS
  LL-VNS exerts protective effects on myocardial I/R injury. Its potential mechanisms involve the suppression of oxidative stress and cellular apoptosis.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Mingxian
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Lilei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Sir Run Run Shaw Hospital, Affiliated to Medical College of Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Songyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D006339:Heart Rate; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D055536:Vagus Nerve Stimulation / Q000379:methods*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D013482:Superoxide Dismutase
keywords: apoptosis; autonomic nerve; ischemia reperfusion injury; oxidative stress; vagus nerve stimulation