Tohoku J. Exp. Med., 2009, 219(3)

High Concentrations of Reactive Oxygen Species in the BAL Fluid Are Correlated with Lung Injury in Rabbits after Hemorrhagic Shock and Resuscitation

MARIOS-KONSTANTINOS TASOULIS,¹ OLGA LIVADITI,¹ MICHALIS STAMATAKOS,² CHARIKLEIA STEFANAKI,² PANTELIS PANERIS,¹ PANAGIOTIS PRIGOURIS,¹ AIKATERINI FLEVARI,¹ NIKOS GOUTAS,³ DIMITRIOS VLACHODIMITROPOULOS,³ VASSILIKI VILLIOTOU⁴ and EMMANUEL E. DOUZINAS¹

¹Third Department of Critical Care Medicine, Athens University School of Medicine, Athens, Greece
²Fourth Department of Surgery, Athens University School of Medicine, Athens, Greece
³Department of Forensic Medicine & Toxicology, Athens University School of Medicine, Athens, Greece
⁴Department of Clinical Biochemistry, Metaxa Cancer Hospital, Piraeus, Greece

Increased levels of cytokines or reactive oxygen species (ROS) in the bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after ischemia/reperfusion. We investigated the correlation of these markers with the degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained by mechanical ventilation, were left untreated (control) or subjected to hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals were re-infused their shed blood for resuscitation. At the end of the experiment, BAL fluid was recovered, in which parameters of oxidative stress and cytokines were measured. Macrophages and malondialdehyde levels were increased (p = 0.043 and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased in the shock animals compared with control (p = 0.009). Production of ROS was significantly enhanced in shock animals compared with controls (p < 0.001). BAL fluid levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals also showed higher histopathological scores that represent severe tissue damage than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04, respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock results in acute lung injury, with enhanced pulmonary oxidative and inflammatory responses. In conclusion, ROS in the BAL fluid are good markers that predict lung injury following hemorrhagic shock and resuscitation.

keywords —— cytokines; flow cytometry; reactive oxygen species; bronchoalveolar lavage; acute lung injury.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 219, 193-199

Correspondence: Emmanuel E. Douzinas, Third Department of Critical Care, EVGENIDION Hospital, 20 Papadiamantopoulou St., Athens 115 28, Greece.

e-mail: edouzin@med.uoa.gr