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

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-alpha, interleukin (IL)-1 beta 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

The effect of hypoxemic resuscitation of hemorrhagic shock on hemodynamic stabilization and inflammatory response: A pilot study in a rat experimental model

Background: Resuscitation of hemorrhagic shock is associated with tissue injury. The effect of hypoxemia during resuscitation was investigated. Methods: Shock was induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to receive either normoxemic (controls, FiO(2) = 21%, n = 14) or hypoxemic (HypRes, FiO(2) = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was assessed through hemodynamic and inflammatory parameters. Another nine rats served to correlate different FiO(2) to the corresponding PaO2. Results: At 60 minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008). The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1-2.1) versus 3.1 (2.4-4.3) fimol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL, (p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values were similar between groups. FiO(2) of 12% induced only a mild hypoxemia (PaO2 similar to 80 mm Hg). Conclusions: Even mild hypoxemia during resuscitation of shock leads to effective hemodynamic stabilization. Key Words: Hemorrhagic shock, Glutathione, Endotoxin, Tumor necrosis factor-alpha, Interferon-gamma, Nitric oxide, Malondialdehyde, Hypoxemic resuscitation