title: Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.
abstract: BACKGROUND
  We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC.
  
  
  METHODS
  MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment.
  
  
  RESULTS
  The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p < 0.001). Pretreatment with calphostin C significantly limited the protection by pressure overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p < 0.001). Calphostin C itself did not significantly affect MI size (25.5 ± 2.4%). Additionally, the hemodynamics, area at risk, and mortality were not significantly different.
  
  
  CONCLUSIONS
  Brief pressure overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Tang
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Exercise and Health Sciences, University of Taipei, Taipei, Taiwan, ROC.
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, ROC.
authors.forename: Shu-Chiung
authors.initials: SC
authors.lastname: Chiang
authors.affiliation: Department of Exercise and Health Sciences, University of Taipei, Taipei, Taiwan, ROC.
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Tseng
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC. Electronic address: chhuang@vghtpe.gov.tw.
authors.forename: Cheng-Hsiung
authors.initials: CH
authors.lastname: Huang
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006352:Heart Ventricles; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D009281:Naphthalenes / Q000494:pharmacology; D011312:Pressure; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009281:Naphthalenes; D011493:Protein Kinase C; C058819:calphostin C
keywords: ischemic preconditioning; myocardial infarction; pressure overload; protein kinase C