Diabetes mellitus and the metabolic syndrome do not abolish, but might reduce, the cardioprotective effect of ischemic postconditioning

ObjectiveIschemic 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).MethodsMice (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.ResultsIn 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).ConclusionsThe 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