BackgroundThe treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored.MethodsFemale Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h.ResultsResuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p<0.05). TxT+H/R-induced significant increase in alanine aminotransferase levels and liver injury were attenuated by EP compared with controls (p<0.05). Local inflammation as shown by increased gene expression of IL-6 and ICAM-1, enhanced ICAM-1 and HMGB1 protein expression and infiltration of the liver with neutrophils were also significantly attenuated by EP compared with controls after TxT+H/R (p<0.05). EP significantly reduced TxT+H/R-induced p65 activation in liver tissue. Survival rates improved by EP from 50% to 70% after TxT+H/R.ConclusionsThese data support the concept that the pronounced local pro-inflammatory response in the liver after blunt chest trauma and hemorrhagic shock is associated with NF-κB. In particular, the beneficial anti-inflammatory effects of ethyl pyruvate seem to be regulated by the HMGB1/NF-κB axis in the liver, thereby, restraining inflammatory responses and liver injury after double hit trauma in the rat.

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This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.

due to their high prevalence, blunt chest trauma (TxT) and hemorrhagic shock have a significant influence on the outcomes of trauma patients, causing severe modulations of the immune system and high mortality rates. Alcohol consumption in trauma patients has a high clinical impact. Studies investigating the timing of alcohol intoxication prior to trauma are limited, although there are two typical scenarios regarding alcohol consumption: Acute ('drink and drive scenario') and sub-acute ('evening binge drinking'). Therefore, the present study investigated the influence of either an acute or sub-acute alcohol-drinking scenario in an in vivo model of TxT and hemorrhagic shock, focusing on liver inflammation and outcomes. At 12 h (sub-acute) or 2 h (acute) before the experiment, female Lewis rats received a single oral dose of alcohol (ethanol, EtOH) or saline (Nacl, ctrl), followed by TxT, hemorrhagic shock (35±3 mm Hg) and resuscitation (H/R). The animals were either sacrificed 2 h later or their survival was determined for 72 h. The results revealed that EtOH induced significant fatty changes in the liver. TxT + H/R-induced increases in the gene expression of interleukin (IL)-6 and intercellular adhesion molecule-1 and the protein expression of tumor necrosis factor (TNF)-α and IL-1β were significantly reduced in both EtOH groups compared with those in the corresponding TxT + H/R ctrl groups. The local presence of IL-10-expressing cells in the liver was significantly increased following TxT + H/R in all groups, although the sub-acute EtOH TxT + H/R group had a significantly higher proportion of IL-10-positive cells compared with all other groups. Stimulating peripheral whole blood with lipopolysaccharide led to significantly lower levels of TNF-α release in the sub-acute EtOH group compared with the levels in all other groups. Significant TxT + H/R-induced increases in liver transaminases and liver damage were most prominent in the sub-acute EtOH group. The TxT + H/R EtOH group exhibited the lowest levels of glucose. There were no significant differences in mortality rate among the TxT + H/R groups. The data obtained indicates that the severity of liver damage following TxT + H/R may depend on the timing of alcohol consumption and severity of trauma, but also on the balance between pro-and anti-inflammatory responses.

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Background: Blunt chest (thoracic) trauma (TxT) and haemorrhagic shock with subsequent resuscitation (H/R) induce strong systemic and local inflammatory response, which is closely associated with apoptotic cell loss and subsequently impaired organ function. The underlying mechanisms are not completely understood, therefore, the treatment of patients suffering from TxT+H/R is challenging. In our recent studies, we have demonstrated local anti-inflammatory effects of ethyl pyruvate (EtP) in lung and liver after TxT+H/R. Here, the therapeutic potential of a reperfusion regime with EtP on the early post-traumatic systemic inflammatory response and apoptotic changes after TxT followed by H/R were investigated. Methods: Female Lewis rats underwent TxT followed by haemorrhagic shock (60 min). Resuscitation was performed with own blood transfusion and either lactated Ringers solution (LR) or LR supplemented with EtP (50 mg/kg). Sham group underwent the surgical procedures. After 2 h blood as well as lung and liver tissues were obtained for analyses. Systemic activation of neutrophils (expression of CD11b and CD62L), leukocyte phagocytosis, apoptosis (caspase-3/7 activation), pyroptosis (caspase-1 activation) and NF-κB p65 activity were assessed. p < 0.05 was considered significant. Results: TxT+H/R-induced systemic activation of neutrophils (increased CD11b and reduced CD62L expression) was significantly reduced by EtP. Trauma-induced delayed neutrophil apoptosis was further reduced by EtP reperfusion but remained unaltered in monocytes. Reperfusion with EtP significantly increased the phagocytizing capacity of granulocytes. Trauma-induced inflammasome activation, which was observed in monocytes and not in neutrophils, was significantly reduced by EtP in both cell entities. NF-κB p65 activation, which was increased in neutrophils and monocytes was significantly decreased in monocytes. Conclusion: TxT+H/R-induced systemic activation of both neutrophils and monocytes concomitant with increased systemic inflammation was reduced by a reperfusion with EtP and was associated with a down-regulation of NF-κB p65 activation.