title: Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway.
abstract: BACKGROUND
  Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice. Here we tested the hypothesis that Na2S therapy would limit the extent of myocardial injury following MI/R when administered at the time of reperfusion.
  
  
  RESULTS
  Diabetic mice (db/db, 12 weeks of age) were subjected to transient myocardial ischemia for a period of 30 minutes followed by reperfusion up to 24 hours. Na2S (0.05 to 1 mg/kg) or saline (vehicle) was administered into the left ventricular lumen at the time of reperfusion. Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels. The reduction in myocardial injury was also associated with a reduction in oxidative stress and a decrease in cleaved caspase-3 expression. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, additional groups of mice were sacrificed during early reperfusion. Hearts were excised and processed for Western blot analysis. These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway.
  
  
  CONCLUSIONS
  These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Lambert
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.
authors.forename: Chad K
authors.initials: CK
authors.lastname: Nicholson
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.
authors.forename: Hena
authors.initials: H
authors.lastname: Amin
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Amin
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Calvert
keywords: Cardioprotection; Diabetes; Hydrogen sulfide; Myocardial Ischemia-reperfusion injury; RISK pathway