Abstract 6249: Selective Activation of Adenosine 2A Receptors Upon Reperfusion, But Not Insulin Treatment, Abrogates the Hyperglycemic Exacerbation of Myocardial Ischemia/Reperfusion Injury in Mice
Introduction: Acute hyperglycemia (HG) is associated with larger infarct size, impaired cardiac function and increased mortality, independent of diabetes. We hypothesized that the anti-inflammatory effects of an adenosine 2A receptor agonist (ATL146e) would prevent acute HG from exacerbating myocardial infarct (MI) size in mice.
Methods: C57BL/6 mice (n=27) underwent 30 min of LAD occlusion followed by 60 min of reperfusion. Acute HG (~400 mg/dl) was induced in 3 of the groups with an IP injection of dextrose (2g/kg body weight) given 40 min prior to LAD occlusion. In one HG group, ATL146e was injected IP 5 min prior to reperfusion at a dose of 10μg/kg. In another HG group, blood glucose was normalized 5 min prior to ischemia with insulin (0.2– 0.5 U/kg, iv).
Results: Risk region size (RR, % of LV) was similar in the 4 groups of mice (p=NS, Fig⇓). In euglycemic B6 mice, infarct size was 34±3% of RR. However, infarct size in HG mice increased by 49% to 50±1% of RR (p<0.05 vs. B6 control). Normalization of blood glucose with insulin had no effect on infarct size (54±4%, p<0.05 vs. B6 control; p=NS vs. HG mice). However, ATL146e given 5 min before reperfusion reduced infarct size in HG mice down to a level 24% smaller than that of B6 control mice (26±4%, p<0.05 vs. HG mice and p=NS vs. B6 mice (Fig⇓).
Conclusions: Acute hyperglycemia (HG) significantly exacerbates infarct size in mice. Normalizing blood glucose before ischemia fails to reverse the deleterious effects of prior HG on MI. However, the increase in MI size caused by HG is completely abolished by selective A2AR activation, suggesting that the exacerbation of MI size by acute HG can be reversed in a clinically-relevant manner.