|Ronchi, Carlos Fernando|
|Fioretto, Jose Roberto|
|Ferreira, Ana Lucia Anjos|
|Berchieri-ronchi, Carolina Bragio|
|Correa, Camila Renata|
|Kurokawa, Climery Suemi|
|Carpi, Mario Ferreira|
|Moraes, Marcos Aurelio|
Submitted to: Journal of Applied Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2012
Publication Date: 4/1/2012
Citation: Ronchi, C., Fioretto, J., Ferreira, A., Berchieri-Ronchi, C.L., Correa, C., Kurokawa, C., Carpi, M., Moraes, M., Yeum, K. 2012. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation. Journal of Applied Physiology. 112(7):1184-1190. Interpretive Summary: Oxidative damage plays an important role in lung injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). This syndrome is a life-threatening lung condition that prevents enough oxygen from getting to the lungs and into the blood. We aimed to identify biomarkers in an animal model to determine the oxidative stress of acute lung injury using two different types of machines that support breathing. Rabbits were provided air with vent using either conventional machine (CMV) or a new machine called high-frequency oscillatory ventilation (HFOV). White blood cells and lung tissue samples were then analyzed for DNA damage. Antioxidant capacity was also measured in blood and lung tissues. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant capacity and lower DNA damage compared with rabbits provided air with conventional vent (CMV) in lung tissue and blood. In addition, higher antioxidant capacity was associated with lower DNA damage in lung tissue. These results indicate that oxidative stress is higher in the rabbits provided air with conventional vent (CMV) than rabbits with the new machine called HFOV.
Technical Abstract: Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.