Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction by activating nicotinamide adenine dinucleotide phosphate oxidase during reperfusion

Zequan Yang, Victor E. Laubach, Brent A. French, Irving L. Kron

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37 Citations (Scopus)

Abstract

Objective: Acute hyperglycemia is independently associated with larger myocardial infarct size in both diabetic and nondiabetic patients. We hypothesized that the oxidative stress imposed by acute hyperglycemia contributes to the exacerbation of infarct size during reperfusion. Methods: C57BL/6 mice underwent 30 minutes of occlusion of the left anterior descending coronary artery followed by 60 minutes of reperfusion. Acute hyperglycemia was induced with an intraperitoneal injection of dextrose (2g/kg body weight) 30 minutes before left anterior descending occlusion. An antioxidant, N-2-mercaptopropionyl glycine, was injected intravenously 2 minutes before the onset of reperfusion at a dose of 20 mg/kg. A nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (50 mg/kg), was applied either before or after the induction of hyperglycemia. Results: Blood glucose level before left anterior descending occlusion was 153 ± 19 mg/dL in control mice and 444 ± 26 mg/dL in hyperglycemic mice (P < .05). Plasma lipid peroxidation product (malondialdehyde) was significantly increased in both control and hyperglycemic mice at 1 hour after reperfusion, and levels of malondialdehyde in hyperglycemic mice were higher than that in control mice (3.38 ± 0.21 vs 2.33 ± 0.12 μmol/L; P < .05). N-2-mercaptopropionyl glycine administered just before reperfusion significantly reduced malondialdehyde levels in both control and hyperglycemic mice (1.21 ± 0.06 and 1.03 ± 0.24 μmol/L). Acute hyperglycemia increased infarct size (percent of risk region) from 34.0 ± 2.7 to 49.4 ± 1.6 (P < .05). N-2-mercaptopropionyl glycine reduced infarct size to 19.5 ± 2.3 in control mice and to 26.2 ± 2.9 in hyperglycemic mice. Apocynin also reduced malondialdehyde levels and infarct size in hyperglycemic mice if administered 5 minutes before injection of dextrose, but not before reperfusion. Conclusion: Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction in mice through activation of nicotinamide adenine dinucleotide phosphate oxidase.

Original languageEnglish (US)
Pages (from-to)723-729
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume137
Issue number3
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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NADPH Oxidoreductases NADH
Myocardial Reperfusion Injury
Obese Mice
Acute Disease
NADP
Inbred C57BL Mouse
Hyperglycemia
Reperfusion
Oxidoreductases
Oxidative Stress
Myocardial Infarction
Malondialdehyde
Glycine
Glucose
Intraperitoneal Injections
Lipid Peroxidation
Blood Glucose
Coronary Vessels
Antioxidants
Body Weight

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{6831566e9f03427492c5093efdec6140,
title = "Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction by activating nicotinamide adenine dinucleotide phosphate oxidase during reperfusion",
abstract = "Objective: Acute hyperglycemia is independently associated with larger myocardial infarct size in both diabetic and nondiabetic patients. We hypothesized that the oxidative stress imposed by acute hyperglycemia contributes to the exacerbation of infarct size during reperfusion. Methods: C57BL/6 mice underwent 30 minutes of occlusion of the left anterior descending coronary artery followed by 60 minutes of reperfusion. Acute hyperglycemia was induced with an intraperitoneal injection of dextrose (2g/kg body weight) 30 minutes before left anterior descending occlusion. An antioxidant, N-2-mercaptopropionyl glycine, was injected intravenously 2 minutes before the onset of reperfusion at a dose of 20 mg/kg. A nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (50 mg/kg), was applied either before or after the induction of hyperglycemia. Results: Blood glucose level before left anterior descending occlusion was 153 ± 19 mg/dL in control mice and 444 ± 26 mg/dL in hyperglycemic mice (P < .05). Plasma lipid peroxidation product (malondialdehyde) was significantly increased in both control and hyperglycemic mice at 1 hour after reperfusion, and levels of malondialdehyde in hyperglycemic mice were higher than that in control mice (3.38 ± 0.21 vs 2.33 ± 0.12 μmol/L; P < .05). N-2-mercaptopropionyl glycine administered just before reperfusion significantly reduced malondialdehyde levels in both control and hyperglycemic mice (1.21 ± 0.06 and 1.03 ± 0.24 μmol/L). Acute hyperglycemia increased infarct size (percent of risk region) from 34.0 ± 2.7 to 49.4 ± 1.6 (P < .05). N-2-mercaptopropionyl glycine reduced infarct size to 19.5 ± 2.3 in control mice and to 26.2 ± 2.9 in hyperglycemic mice. Apocynin also reduced malondialdehyde levels and infarct size in hyperglycemic mice if administered 5 minutes before injection of dextrose, but not before reperfusion. Conclusion: Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction in mice through activation of nicotinamide adenine dinucleotide phosphate oxidase.",
author = "Zequan Yang and Laubach, {Victor E.} and French, {Brent A.} and Kron, {Irving L.}",
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pages = "723--729",
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TY - JOUR

T1 - Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction by activating nicotinamide adenine dinucleotide phosphate oxidase during reperfusion

AU - Yang, Zequan

AU - Laubach, Victor E.

AU - French, Brent A.

AU - Kron, Irving L.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Objective: Acute hyperglycemia is independently associated with larger myocardial infarct size in both diabetic and nondiabetic patients. We hypothesized that the oxidative stress imposed by acute hyperglycemia contributes to the exacerbation of infarct size during reperfusion. Methods: C57BL/6 mice underwent 30 minutes of occlusion of the left anterior descending coronary artery followed by 60 minutes of reperfusion. Acute hyperglycemia was induced with an intraperitoneal injection of dextrose (2g/kg body weight) 30 minutes before left anterior descending occlusion. An antioxidant, N-2-mercaptopropionyl glycine, was injected intravenously 2 minutes before the onset of reperfusion at a dose of 20 mg/kg. A nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (50 mg/kg), was applied either before or after the induction of hyperglycemia. Results: Blood glucose level before left anterior descending occlusion was 153 ± 19 mg/dL in control mice and 444 ± 26 mg/dL in hyperglycemic mice (P < .05). Plasma lipid peroxidation product (malondialdehyde) was significantly increased in both control and hyperglycemic mice at 1 hour after reperfusion, and levels of malondialdehyde in hyperglycemic mice were higher than that in control mice (3.38 ± 0.21 vs 2.33 ± 0.12 μmol/L; P < .05). N-2-mercaptopropionyl glycine administered just before reperfusion significantly reduced malondialdehyde levels in both control and hyperglycemic mice (1.21 ± 0.06 and 1.03 ± 0.24 μmol/L). Acute hyperglycemia increased infarct size (percent of risk region) from 34.0 ± 2.7 to 49.4 ± 1.6 (P < .05). N-2-mercaptopropionyl glycine reduced infarct size to 19.5 ± 2.3 in control mice and to 26.2 ± 2.9 in hyperglycemic mice. Apocynin also reduced malondialdehyde levels and infarct size in hyperglycemic mice if administered 5 minutes before injection of dextrose, but not before reperfusion. Conclusion: Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction in mice through activation of nicotinamide adenine dinucleotide phosphate oxidase.

AB - Objective: Acute hyperglycemia is independently associated with larger myocardial infarct size in both diabetic and nondiabetic patients. We hypothesized that the oxidative stress imposed by acute hyperglycemia contributes to the exacerbation of infarct size during reperfusion. Methods: C57BL/6 mice underwent 30 minutes of occlusion of the left anterior descending coronary artery followed by 60 minutes of reperfusion. Acute hyperglycemia was induced with an intraperitoneal injection of dextrose (2g/kg body weight) 30 minutes before left anterior descending occlusion. An antioxidant, N-2-mercaptopropionyl glycine, was injected intravenously 2 minutes before the onset of reperfusion at a dose of 20 mg/kg. A nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (50 mg/kg), was applied either before or after the induction of hyperglycemia. Results: Blood glucose level before left anterior descending occlusion was 153 ± 19 mg/dL in control mice and 444 ± 26 mg/dL in hyperglycemic mice (P < .05). Plasma lipid peroxidation product (malondialdehyde) was significantly increased in both control and hyperglycemic mice at 1 hour after reperfusion, and levels of malondialdehyde in hyperglycemic mice were higher than that in control mice (3.38 ± 0.21 vs 2.33 ± 0.12 μmol/L; P < .05). N-2-mercaptopropionyl glycine administered just before reperfusion significantly reduced malondialdehyde levels in both control and hyperglycemic mice (1.21 ± 0.06 and 1.03 ± 0.24 μmol/L). Acute hyperglycemia increased infarct size (percent of risk region) from 34.0 ± 2.7 to 49.4 ± 1.6 (P < .05). N-2-mercaptopropionyl glycine reduced infarct size to 19.5 ± 2.3 in control mice and to 26.2 ± 2.9 in hyperglycemic mice. Apocynin also reduced malondialdehyde levels and infarct size in hyperglycemic mice if administered 5 minutes before injection of dextrose, but not before reperfusion. Conclusion: Acute hyperglycemia enhances oxidative stress and exacerbates myocardial infarction in mice through activation of nicotinamide adenine dinucleotide phosphate oxidase.

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