Cardiopulmonary bypass exacerbates oxidative stress but does not increase proinflammatory cytokine release in patients with diabetes compared with patients without diabetes:: Regulatory effects of exogenous nitric oxide

Background: Cardiopulmonary bypass induces oxidative stress and a whole-body inflammatory reaction that are believed to increase surgical morbidity. Objectives: Our goal was to investigate the effect of nitric oxide supplementation on bypass-induced oxidative stress and inflammatory reaction in patients with and without diabetes undergoing elective coronary bypass graft surgery. Methods: Patients with and without diabetes were randomized to receive an infusion of saline solution or the nitric oxide donor nitroglycerin at 1 mu g . kg(-1) . min(-1) starting 10 minutes before the initiation of cardiopulmonary bypass and then maintained for 4 hours (n = 10 per group). Serial blood samples were taken at various intervals and plasma was analyzed for markers of oxidative stress (lipid hydroperoxides, protein carbonyls, and protein nitrotyrosine) and inflammation (complement C3a, elastase, interleukin 8, and tumor necrosis factor alpha). Results: Cardiopulmonary bypass significantly increased lipid hydroperoxides, protein carbonyls, protein nitrotyrosine, complement C3a, elastase, soluble E-selectin, interleukin 8, and tumor necrosis factor a in both groups. Infusion of nitroglycerin significantly reduced the increase in lipid hydroperoxides and protein carbonyls in patients who have diabetes without affecting levels in patients without diabetes. Nitroglycerin infusion markedly reduced protein nitrotyrosine and tumor necrosis factor alpha levels in both groups. In contrast, nitroglycerin infusion significantly increased C3a in patients without diabetes and increased elastase and interleukin 8 levels in patients with diabetes. Conclusions: Cardiopulmonary bypass induces a greater oxidative stress in patients with diabetes than in those without diabetes, and the inflammatory reaction is qualitatively different in the 2 groups of patients. In addition, nitroglycerin reduces oxidative stress in patients with diabetes and differentially affects the inflammatory response to bypass both in patients with and in those without diabetes. The results have important implications with respect to the use of nitric oxide donors during cardiopulmonary bypass.