Systemic inflammatory response does not correlate with acute lung injury associated with mechanical ventilation strategies in normal lungs.

Background: Mechanical ventilation (MV) can lead to ventilator-induced lung injury secondary to trauma and associated increases in pulmonary inflammatory cytokines. There is controversy regarding the associated systemic inflammatory response. In this report, we demonstrate the effects of MV on systemic inflammation.

Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

Background: Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.

Methods/principal Findings: The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury.

The anatomic sites of disruption of the mucus layer directly correlate with areas of trauma/hemorrhagic shock-induced gut injury.

Background: The intestinal mucus layer is an important but understudied component of the intestinal barrier. Consequently, we tested the hypothesis that the anatomic sites of loss of the mucus layer would directly correlate with sites of intestinal villous injury after trauma-hemorrhagic shock (T/HS) and may, therefore, serve as loci of gut barrier failure. Consequently, to investigate this hypothesis, we used Carnoy's fixative solution to prepare fixed tissue blocks where both the gut morphology and the mucus layer could be assessed on the same tissues slides.

Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.

Background: Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs.

Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.

Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate.

Mesenteric lymph duct ligation improves survival in a lethal shock model.

The goal of this study was to test the hypothesis that factors released from the gut and carried in the mesenteric lymph contribute to mortality in a lethal gut I/R model. To test this hypothesis, a lethal splanchnic artery occlusion (SAO) shock model was used in male Sprague-Dawley rats. In the first set of experiments, ligation of the mesenteric lymph duct (LDL), which prevents gut-derived factors carried in the intestinal lymphatics from reaching the systemic circulation, significantly improved 24-h survival after a 20-min SAO insult (0% vs.

Trauma-shock-induced gut injury and the production of biologically active intestinal lymph is abrogated by castration in a large animal porcine model.

Although small animal rodent studies indicate that there is a sexual dimorphism in the resistance to organ injury after trauma-hemorrhagic shock (T/HS), confirmatory studies are largely lacking in more clinically relevant large animal species. Thus, we tested the hypothesis that castration would reduce the susceptibility of adult minipigs to gut injury and abrogate the production of biologically active intestinal (mesenteric) lymph after T/HS. The hemodynamic response to T/HS was similar between castrated and noncastrated minipigs.