Journal
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Volume 145, Issue 6, Pages 1595-1602Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jtcvs.2013.02.016
Keywords
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Funding
- Research Foundation-Flanders
- KU Leuven CoE MoSAIC
- EC FP7 ITN BetaTrain [289932]
- [G.0966.11]
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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.
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