title: Diabetes mellitus and the metabolic syndrome do not abolish, but might reduce, the cardioprotective effect of ischemic postconditioning.
abstract: OBJECTIVE
  Ischemic preconditioning fails to protect the diabetic heart against lethal reperfusion injury. Because the pathways of ischemic pre- and postconditioning partially overlap, we evaluated the cardioprotective effect of ischemic postconditioning in mouse models of type 2 diabetes (ObOb) and the metabolic syndrome (DKO).
  
  
  METHODS
  Mice (C57BL/6J, ObOb, and DKO; aged 24 weeks; n = 24, n = 28, and n = 18, respectively) underwent reperfusion after 30 minutes of coronary occlusion with or without ischemic postconditioning (3 cycles of 10 seconds reperfusion-reocclusion). Left ventricular contractility and infarct size were assessed 60 minutes later with pressure conductance analysis and 2,3,5-triphenyl-tetrazolium chloride staining, respectively. In a second cohort (C57BL/6J and DKO; aged 12 weeks; n = 31 and n = 24, respectively) cardiac cine magnetic resonance imaging was performed after 1 and 10 weeks, followed by pressure conductance analysis and Sirius red staining.
  
  
  RESULTS
  In the C57BL6/J mice, the infarct size was lower (40%, P < 10(-5)) and the load independent preload recruitable stroke work was greater after ischemic postconditioning (P < .05). In the ObOb and DKO mice, ischemic postconditioning reduced the infarct size by 24% (P < 10(-5)). In the C57BL/6J mice, the ejection fraction was greater and the myocardial mass was lower 10 weeks after ischemic postconditioning (P < .05). Tagging grid deformation was increased after ischemic postconditioning in both infarcted and remote areas. After ischemic postconditioning, the survival and ejection fraction were greater in the DKO mice (67% vs 17% and 44% ± 11% vs 59% ± 2%, P < .05 for both), and the collagen content was lower for both C57BL/6J and DKO mice (P < .05 for both).
  
  
  CONCLUSIONS
  The cardioprotective effect of ischemic postconditioning was sustained in C57BL/6J mice after 10 weeks and protected against adverse left ventricular remodeling. In mouse models of type 2 diabetes, protection against lethal reperfusion injury is present, leading to increased survival after ischemia and reperfusion.
authors.affiliation: Department of Cardiovascular Sciences, Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Oosterlinck
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.forename: Vincent
authors.initials: V
authors.lastname: Geldhof
authors.forename: Ines
authors.initials: I
authors.lastname: Nevelsteen
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D057775:Ischemic Postconditioning; D019157:Ischemic Preconditioning, Myocardial; D008279:Magnetic Resonance Imaging / Q000379:methods; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D015996:Survival Rate