Immunemodulatory effects of hypertonic saline in hemorrhagic shock: In vivo alterations of neutrophil-endothelial dynamics and vascular permeability result in attenuated tissue injury.

摘要

Multiple organ dysfunction is the most common cause of late mortality in trauma patients. Despite adequate resuscitation, hemorrhagic shock may progress to a state of profound systemic inflammation where the polymorphonuclear neutrophil (PMN) plays a key role. Resuscitation with hypertonic saline (HTS) may modulate the host inflammatory response in hemorrhagic shock.; A murine hemorrhagic shock model evaluated by cremaster intravital microscopy demonstrated significant in vivo attenuation of neutrophil rolling and adhesion to endothelium (EC) immediately after resuscitation with HTS, as compared to Ringer's lactate (RL). Concurrently, macromolecular leakage from the same post capillary venules was 45% lower in HTS animals.; To better simulate clinical conditions, the model was transformed to recreate two-hit conditions by subjecting resuscitated animals to a subsequent mimicked pulmonary infection. Attenuated neutrophil adhesion to endothelium in HTS animals persisted 5 and 22 hours after resuscitation. Additionally, compared to RL, HTS resuscitation reduced neutrophil lung sequestration (by the myeloperoxidase assay) and neutrophil lung transmigration (by histologic analysis) one day after resuscitation. HTS resuscitation also tended to improve cremaster and lung histologic injury a day after resuscitation conferring a 50% survival advantage for that time interval.; To determine if reductions in tissue injury were due to the ability of HTS to functionally block neutrophil adhesion to endothelium, another variation to the two-hit model was developed. Two additional groups were added to evaluate if supplementation of standard fluid resuscitation with anti adhesion monoclonal antibodies (anti-CD11b and anti-ICAM-1) would reproduce the effects of HTS alone. Although early EC/PMN interactions and 24-hour lung PMN accumulation were similarly attenuated by either HTS alone or RL with anti adhesion blockade, only HTS alone definitely reduced early in vivo macromolecule leakage, and one day lung histologic injury.; Hemorrhagic shock resuscitation with hypertonic saline reduces neutrophil activation and interactions with microvascular endothelium resulting in diminished lung PMN sequestration persisting well beyond the initial resuscitation phase. Yet the anti-adhesive effects of HTS are not essential for HTS-mediated reductions in tissue injury and organ dysfunction. Hypertonic resuscitation may prove to be an immunomodulatory therapy useful in critically ill trauma victims, the precise mechanisms of which need further elucidation.