Role of Hemorrhagic Shock in Experimental Polytrauma.

Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers.

Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI).

Background: Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma.

Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage.

Pulmonary Fas activation is essential in the pathogenesis of the acute respiratory distress syndrome. It remains unclear whether Fas-induced lung injury is dependent on neutrophils or mainly triggered by epithelial cell apoptosis. The contribution of lung epithelial cells (LEC) and alveolar macrophages (AM) remains elusive.

Apoptotic and inflammatory signaling via Fas and tumor necrosis factor receptor I contribute to the development of chest trauma-induced septic acute lung injury.

Background: Direct acute lung injury (ALI) is still associated with a high mortality, whereas the underlying pathomechanisms are not yet fully understood. In this regard, epithelial cell death in the lungs has been attributed an important role in the pathogenesis of this clinical entity. Based on this background here, we hypothesized that signaling through Fas and tumor necrosis factor receptor 1 (TNFR-1) is involved in mediating apoptosis and inflammation in chest trauma induced septic ALI.

Silencing of fas, fas-associated via death domain, or caspase 3 differentially affects lung inflammation, apoptosis, and development of trauma-induced septic acute lung injury.

Activation of Fas signaling is a potentially important pathophysiological mechanism in the development of septic acute lung injury (ALI). However, so far the optimal targets within this signaling cascade remain elusive. Thus, we tested the hypothesis that in vivo gene silencing of Fas, Fas-associated via death domain (FADD), or caspase 3 by intratracheal administration of small interfering RNA would ameliorate ALI in a clinically relevant double-hit mouse model of trauma induced septic lung injury.

Role of activated neutrophils in chest trauma-induced septic acute lung injury.

More than 50% of severely injured patients have chest trauma. Second insults frequently result in acute lung injury (ALI), with sepsis being the main underlying condition. We aimed to develop a standardized, reproducible, and clinically relevant double-hit mouse model of ALI induced by chest trauma and polymicrobial sepsis and to investigate the pathophysiologic role of activated neutrophils.