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| Acute Hyperglycemia Enhances Oxidative Stress During Reperfusion and Exacerbates Myocardial Infarction |
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Zequan Yang1, Victor E. Laubach1, Brent A. French2, Irving L. Kron1; 1Surgery, University of Virginia Health System, Charlottesville, VA; 2Biomedical Engineering, University of Virginia, Charlottesville, VA Objective: Clinical evidence has shown that acute hyperglycemia is independently associated with larger myocardial infarct size (IF) in both diabetic and non-diabetic patients. Admission hyperglycemia is an independent risk factor for post-operative mortality in non-diabetic patients after coronary artery bypass grafting (CABG). We hypothesize that the oxidative stress imposed by acute hyperglycemia contributes to the exacerbation in IF during reperfusion, such as following CABG. Methods: An in vivo mouse model with myocardial ischemia/reperfusion injury was employed. C57BL/6 mice underwent 30 min of LAD occlusion followed by 60 min of reperfusion. Acute hyperglycemia was induced with an IP injection of dextrose (2 g/kg body weight) 30 min prior to the occlusion of LAD. An anti-oxidant, N-2-mercaptopropionyl glycine (MPG), was injected IV 2 min before and 1 min after the onset of reperfusion in two equal doses of 20 mg/kg. At the end of 60 min reperfusion, plasma lipid peroxidation products (malondialdehyde, MDA) was measured using ELISA and myocardial infarct size was determined using TTC staining. Results: The blood glucose level before LAD occlusion was 195±6.6 mg/dl in control mice and 464±24 mg/dl in hyperglycemic (HG) mice (p<0.05). There were no statistical differences in risk region size (RR, % of LV) among the 4 groups of mice. In Control mice, IF, (% of RR) was 34.0±2.7%. However, IF in HG mice increased by 49% to 50.5±1.4% (p<0.05 vs. Control). Administration of MPG to control mice (MPG group) reduced IF to 22.8±5.3, (33% reduction from Control). Administration of MPG to HG mice (HG+MPG group) reduced IF to 28.6±5.6 (a 43% reduction, p<0.05 vs. HG mice, Fig.). In Control mice, plasma MDA was significantly increased during reperfusion to 2.38±0.07 mM from the 0.71±0.02 mM measured in Sham mice (p<0.05). Acute hyperglycemia further increased plasma MDA to 2.96±0.07 mM (p=0.08 vs. Control). Treatment with MPG significantly reduced the plasma MDA in both Control and HG mice to 1.21±0.14 mM and 1.03±0.02 mM, respectively (p<0.05 vs. either Control or HG mice). Conclusion: Acute hyperglycemia significantly increases oxidative stress and exacerbates myocardial IF in mice. The efficacy of MPG in reducing hyperglycemic IF when administered only minutes prior to and/or after reperfusion demonstrate that this can be accomplished in a practical and clinically-relevant manner. This manipulation could result in reducing the impact of acute hyperglycemia on perioperative myocardial infarction.  Back to 88th Annual Meeting Back to Program Outline |
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