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Oxidation of myocardial glutathione increases susceptibility to ventricular arrhythmia in the aged diabetic heart
Author(s) -
Sloan Ruben C,
Frasier Chad,
Anderson Ethan,
Wingard Christopher,
Brown David A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.597.5
Subject(s) - medicine , diabetes mellitus , ventricular fibrillation , cardiology , glutathione , endocrinology , chemistry , biochemistry , enzyme
Recent work from our group using young healthy animals has shown that overwhelming cellular anti‐oxidant defenses can induce ventricular arrhythmia under normoxic conditions. The purpose of this study was to determine whether aged (22 ± 1 months) diabetic hearts were more susceptible to ventricular arrhythmia following treatment with diamide, a thiol‐oxidizing agent. Male Zucker Diabetic Fatty rats had higher resting glucose levels (476 ± 17 mg/dL) than their lean non‐diabetic counterparts (126 ± 9 mg/dL; P < 0.05). Hearts were excised and perfused with Krebs‐Henseleit buffer containing 200 uM diamide. Baseline left ventricular developed pressures were significantly lower in diabetic rats (55 ± 11mmHg) than non‐diabetic counterparts (89 ± 15mmHg; P < 0.05), and this functional difference persisted 10 minutes through diamide treatment (59.97 ± 10.57 mmHg vs. 105.1 ± 19.36 mmHg after 10 minutes of diamide, respectively; P < 0.05). After diamide administration, diabetic hearts transitioned into ventricular arrhythmias much sooner than non‐diabetic hearts. Time to ventricular fibrillation was 21.69 ± 1.456 min in diabetic hearts vs. 30.44 ± 1.711 min in non‐diabetic hearts (P < 0.05). These results demonstrate that the aged diabetic heart is more susceptible to development of fatal arrhythmia when presented with an oxidant challenge, which has broad implications for cardiac disease in diabetics.