title: Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism.
abstract: OBJECTIVE
  Physical activity has been shown to improve cardiovascular function and to be beneficial to type 2 diabetic patients. However, the effects of aerobic exercise (AE) on myocardial ischemia/reperfusion (MI/R) are largely unclear. Therefore, the aims of the present study were to determine whether long-term AE can protect the heart against I/R injury, and if so, to investigate the underlying mechanism.
  
  
  METHODS
  Adult male Sprague-Dawley rats were randomly subjected to 8 weeks of either sedentary or free-loading swimming exercise (3 h/day, 5 d/week). Then the animals were subjected to 30 min MI followed by 4 h R. Arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the whole MI/R procedure. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (TUNEL analysis) were determined in a blinded manner.
  
  
  RESULTS
  MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with sedentary group, rats subjected to 8 weeks of AE showed protection against MI/R as evidenced by reduced myocardial infarction (26.8 +/- 1.5% vs. 35.3 +/- 2.4%, n = 8, P < 0.05), inhibited cardiomyocyte apoptosis (decreased apoptotic index (12.4 +/- 1.1% vs. 21.0 +/- 1.7%, n = 8, P < 0.01) and decreased myocardial caspase-3 activity), decreased plasma CK and LDH activities and improved recovery of cardiac systolic/diastolic function (including LVSP and +/-LVdP/dt) at the end of R. Moreover, exercise resulted in 1.7-fold, 2.5-fold and 2.5-fold increases in Akt expression, Akt phosphorylation and glycogen synthase kinase-3beta phosphorylation in I/R myocardium, respectively (n = 3, all P < 0.05). More importantly, treatment with wortmannin, a PI3 kinase inhibitor, 15 min before R not only significantly blocked Akt phosphorylation (P < 0.05) in exercise rats, but also abolished long-term AE-induced cardioprotection for the I/R heart as manifested by increased apoptosis and myocardial infarction, and reduced cardiac function.
  
  
  CONCLUSIONS
  Long-term AE exerts cardioprotective effect against MI/R injury, including anti-cardiomyocyte apoptosis, which is at least partly via PI3 kinase-dependent and Akt-mediated mechanism.
authors.affiliation: Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kun-Ru
authors.initials: KR
authors.lastname: Zhang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Quan-Jiang
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Li
authors.forename: Qiu-Jun
authors.initials: QJ
authors.lastname: Yu
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Guo
authors.forename: Hai-Chang
authors.initials: HC
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D006321:Heart / Q000502:physiology; D006836:Hydro-Lyases / Q000097:blood; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase; C505410:Casp3 protein, rat; D053148:Caspase 3; D006836:Hydro-Lyases; C045581:lactate dehydratase; D000077191:Wortmannin