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39 Endogenous protection against myocardial ischaemia-reperfusion injury in the diabetic heart
  1. H J Whittington,
  2. C P McLaughlin,
  3. D J Hausenloy,
  4. D M Yellon,
  5. M M Mocanu
  1. The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, UCL, UK

Abstract

There are contradictory data in the literature regarding the susceptibility of the diabetic heart to ischaemia/reperfusion injury and the initiation of cardioprotection by activating endogenous prosurvival mechanisms. We hypothesise that the diabetic heart may be more susceptible to injury but still amenable to protection. Ex vivo hearts from diabetic rats (Goto–Kakizaki), subjected to 35 min ischaemia and 60 min reperfusion (IRI), were randomly assigned to the following groups: (a) control (as above), (b) preconditioned with three cycles of 5 min ischaemia and 10 min reperfusion prior to IRI, (c) subjected to different ischaemic durations (20 or 45 min), or (d) treated with metformin for 4 weeks prior to IRI; (a)–(c) experiments were also performed in normoglycaemic Wistar rat hearts. The end points of injury were: infarct size measurements (a−d), mitochondria assessment using electron microscopy (a+d), and Western blot analyses (a+d). The Goto–Kakizaki diabetic hearts subjected to 20 min or 35 min ischaemia develop similar infarct sizes, 32.7%±2.3 and 30.9%±2.1, respectively. In contrast, the non-diabetic Wistar hearts, following the same protocols give rise to infarct volumes of 21.1%±2.2 and 54.5%±2.5, respectively. In addition the diabetic heart could not be preconditioned by the protocol we used. However, the diabetic hearts treated with metformin developed significantly less infarction than the control hearts (47.8%±2.1 vs 16.6%±1.7) after IRI, seem to possess larger and fewer mitochondria and demonstrate a significant increase in PGC-1α (7.5±2.0 vs 2.8±0.5 densitometry arbitrary units). These findings suggest that the diabetic heart may be more susceptible to infarction, however pro survival mechanisms can still be initiated to provide protection against ischaemia/reperfusion injury.

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