OBJECTIVES: Acute lung injury and acute respiratory distress syndrome (ALI, ARDS) are well-known complications of cardiac and major vascular surgery. ARDS is associated with high mortality and no effective treatment is available. Protective effects of antioxidants or nitric oxide (NO) in experimental studies were not confirmed in clinical trials, but the potential beneficial effects of their combination are poorly known. This study was designed to investigate whether concomitant administration of NO donor and antioxidants has synergic effects on lung protection in ALI. DESIGN: ALI was induced in rats by intestinal ischemia-reperfusion. Superoxide dismutase and catalase were administered as antioxidants and arginine as NO donor. Lung wet-dry ratio, MPO activity, tissue-air ratio, airspace hemorrhage and serum TNF-alpha were used as parameters of lung injury and systemic inflammation. RESULTS: Antioxidants and arginine significantly reduced lung damage when administered separately. However, concomitant administration of antioxidants and arginine abolished the protective effects and enhanced systemic inflammation. CONCLUSIONS: Our data suggests that antioxidants and NO in combination should be avoided in clinical practice.
OBJECTIVES:Acute lung injury and acute respiratory distress syndrome (ALI, ARDS) are well-known complications of cardiac and major vascular surgery. ARDS is associated with high mortality and no effective treatment is available. Protective effects of antioxidants or nitric oxide (NO) in experimental studies were not confirmed in clinical trials, but the potential beneficial effects of their combination are poorly known. This study was designed to investigate whether concomitant administration of NO donor and antioxidants has synergic effects on lung protection in ALI. DESIGN: ALI was induced in rats by intestinal ischemia-reperfusion. Superoxide dismutase and catalase were administered as antioxidants and arginine as NO donor. Lung wet-dry ratio, MPO activity, tissue-air ratio, airspace hemorrhage and serum TNF-alpha were used as parameters of lung injury and systemic inflammation. RESULTS: Antioxidants and arginine significantly reduced lung damage when administered separately. However, concomitant administration of antioxidants and arginine abolished the protective effects and enhanced systemic inflammation. CONCLUSIONS: Our data suggests that antioxidants and NO in combination should be avoided in clinical practice.
Authors: Dinesh Kumar; Billy G Branch; Christopher B Pattillo; Jay Hood; Stephen Thoma; Stephen Simpson; Sandra Illum; Neeraj Arora; John H Chidlow; Will Langston; Xinjun Teng; David J Lefer; Rakesh P Patel; Christopher G Kevil Journal: Proc Natl Acad Sci U S A Date: 2008-05-27 Impact factor: 11.205