title: Brief left ventricular pressure overload reduces myocardial apoptosis.
abstract: BACKGROUND
  Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved.
  
  
  METHODS
  MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions.
  
  
  RESULTS
  Brief LVPO and ischemic preconditioning significantly decreased MI size (P < 0.001). Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P < 0.001), little or no DNA laddering, and reduced caspase-3 activation (P < 0.01). Moreover, brief pressure overload significantly increased Bcl-2 (P < 0.001) and decreased Bax (P < 0.001) and p53 (P < 0.01). Akt phosphorylation was significantly increased by brief pressure overload (P < 0.001), whereas c-Jun N-terminal kinase phosphorylation was significantly decreased (P < 0.001). Hemodynamics, area at risk, and mortality did not differ significantly among groups.
  
  
  CONCLUSIONS
  Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation.
authors.affiliation: Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Emergency Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Hsien-Hao
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Chang-Chi
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Institute of Hospital and Health Care Administration, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shu-Chiung
authors.initials: SC
authors.lastname: Chiang
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Chest Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shi-Chuan
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan; Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Jin-Ching
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan. Electronic address: chhuang@vghtpe.gov.tw.
authors.forename: Cheng-Hsiung
authors.initials: CH
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D017725:Ventricular Pressure / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Apoptosis; Brief left ventricular pressure overload; Cell signaling; Ischemic preconditioning; Myocardial infarct