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.

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Matata BM, Galinanes M

J Thorac Cardiovasc Surg. 2000 Jul;120(1):1-11.

PubMed ID

10884648 [ View in PubMed

]

Abstract

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 microg. 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 alpha 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.

DrugBank Data that Cites this Article

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Nitroglycerin	Approved Investigational	TNF	7124	decreased	Nitroglycerin results in decreased expression of TNF protein	6p21.33
Nitroglycerin	Approved Investigational	C3	718	increased	Nitroglycerin results in increased expression of C3 protein alternative form	19p13.3
Nitroglycerin	Approved Investigational	CXCL8	3576	increased	Nitroglycerin results in increased expression of CXCL8 protein	4q13.3
Nitroglycerin	Approved Investigational	ELANE	1991	increased	Nitroglycerin results in increased expression of ELANE protein	19p13.3