Abstract
Chronic hyperglycemia has been associated with increased oxidative stress in skeletal muscle and sympathetic nerve dysfunction. We investigated the effect of chronic hyperglycemia on the myocardium of patients with uncontrolled diabetes (UD) compared with patients with well-controlled diabetes (CD) and patients without diabetes (ND) after cardioplegic cardiopulmonary bypass (CP/CPB) with acute intraoperative glycemic control. Atrial tissue and serum were collected from 47 patients (ND=18 with glycated hemoglobin [HbA1c] of 5.8±0.2; CD=8 with HbA1c of 6.1±0.1; with UD=21 with HbA1c=9.6±0.5) before and after CP/CPB for immunoblotting, protein oxidation assays, immunohistochemical evaluation, and microarray analysis. The uncontrolled group had increased total protein oxidation (p<0.05) and decreased levels of antioxidative enzyme manganese superoxide dismutase (MnSOD) (p<0.05) after CP/CPB compared with the controlled group. Collagen staining revealed increased fibrosis in patients with UD (p<0.05) compared with patients with CD and patients without diabetes. The uncontrolled group also showed a decrease in the neurogenic and angiogenic markers nerve growth factor (NGF) (p<0.05), neurotrophin (NT)-3 (p<0.05), and platelet-derived growth factor (PDGF)-β (p<0.05) compared with the other groups after CP/CPB. Atrial and serum microarray analysis showed increased oxidative stress and sympathetic nerve damage, increased fibrosis, and a decrease in angiogenesis in patients with UD (p<0.03) compared with patients without diabetes. CP/CPB led to higher oxidative stress in patients with UD before surgical intervention, even after normal glucose levels were maintained intraoperatively. Thus, controlled HbA1C in addition to acute intraoperative glucose control may be a more suitable end point for patients with diabetes undergoing cardiac operations.
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