Acute lung injury after hemorrhagic shock is dependent on gut injury and sex

Recent studies have established gut-derived lymph rather than portal blood as the major source of toxic mediators after hemorrhagic shock that causes distant organ injury. Similarly, emerging data have identified sex as a maj or modifier of the response to injury and illness. Thus we tested the hypot hesis that female rats would be more resistant to shock-induced lung injury than male rats because females are more resistant to shock-induced gut inj ury and produce mesenteric lymph that is less toxic to endothelial cells. M ale and female rats were subjected to sham or hemorrhagic shock and lung pe rmeability was quantitated by Evans blue dye and protein extravasation into the alveolar space. Next, mesenteric lymph collected from shocked and sham -shocked rats of both sexes was incubated with human umbilical vein endothe lial cells (HUVECs) and assayed for toxicity. Trypan blue dye exclusion and the release of lactate dehydrogenase assessed HUVEC viability and injury r espectively. Lastly, sections of the terminal ileum were histologically exa mined for evidence of shock-induced mucosal injury. Male rats but not femal e rats subjected to hemorrhagic shock had evidence of increased lung permea bility and produced mesenteric lymph that was cytotoxic to HUVECs. Shock ca used gut injury in the male rats whereas histological evidence of gut injur y was not observed in the female rats. Hemorrhagic shock-induced lung injur y depends on gut injury and mesenteric lymph appears to be the route by whi ch gut-derived toxic factors exit the gut to cause lung injury. The resista nce of female rats to shock-induced lung injury appears to be secondary to their resistance to shock-induced gut injury.