title: Recombinant human-activated protein C inhibits cardiomyocyte apoptosis in a rat model of myocardial ischemia-reperfusion.
abstract: OBJECTIVE
  Myocardial apoptosis is recognized as a major mechanism of cell death during ischemia-reperfusion. In this study, we assessed the hypothesis that activated protein C may have a cardioprotective effect via preventing apoptosis in a rat model of myocardial ischemia-reperfusion.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were anesthetized, instrumented for hemodynamic measurements and ventilated mechanically. Twenty rats were subjected to 20 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. They were randomly assigned to receive intravenous Ringer lactate (vehicle) or activated protein C (2 mg/kg/h) 10 min after occlusion and during reperfusion. The other 10 rats were sham-operated. At the end of the reperfusion period, serum samples were obtained for evaluation of creatine kinase, C-reactive protein and tumor necrosis factor-alpha. Apoptosis was measured quantitatively by the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling method.
  
  
  RESULTS
  Serum creatine kinase, C-reactive protein and tumor necrosis factor-alpha values and percentage of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- positive myocyte nuclei demonstrated negligible myocardial injury in sham-operated controls. During reperfusion, mean arterial pressures were significantly higher in activated protein C-treated rats than in the control group (68.2+/-10.3 vs. 55.4+/-11.6 mmHg, P=0.01). Number of apoptotic cells was significantly reduced from 47.7 to 24.8% with activated protein C administration (P=0.008). No difference was seen between activated protein C-treated and untreated animals with respect to creatine kinase, C-reactive protein and tumor necrosis factor-alpha levels.
  
  
  CONCLUSIONS
  Treatment with activated protein C significantly improved hemodynamics after ischemia-reperfusion and reduced ischemia-reperfusion-induced myocardial apoptosis in rats.
authors.affiliation: Department of Cardiology, Baskent University Faculty of Medicine, Ankara, Turkey. baharpirat@gmail.com
authors.forename: Bahar
authors.initials: B
authors.lastname: Pirat
authors.forename: Haldun
authors.initials: H
authors.lastname: Muderrisoglu
authors.forename: Muge Tecder
authors.initials: MT
authors.lastname: Unal
authors.forename: Handan
authors.initials: H
authors.lastname: Ozdemir
authors.forename: Aylin
authors.initials: A
authors.lastname: Yildirir
authors.forename: Muammer
authors.initials: M
authors.lastname: Yucel
authors.forename: Suna
authors.initials: S
authors.lastname: Turkoglu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D011486:Protein C / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D011486:Protein C; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D003402:Creatine Kinase