IMMUNOMODULATORY EFFECTS OF HYPERTONIC RESUSCITATION ON THE DEVELOPMENT OF LUNG INFLAMMATION FOLLOWING HEMORRHAGIC-SHOCK

Hypertonic resuscitation fluids are known to be effective in restoring circulating volume in the hypovolemic trauma patient, Previous studie s have suggested that hypertonicity might exert effects on immune cell s leading to an altered host response. The present studies evaluated t he effect of hypertonic resuscitation on the development of lung injur y in a hemorrhagic shuck model in which antecedent shock primes for in creased lung neutrophil sequestration in response to intratracheal LPS . Resuscitation with hypertonic saline significantly reduced albumin l eak, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathologic injury compared with resuscitation with Ringer's lact ate. Both in vivo and in vitro data suggest that this beneficial effec t mag be related to altered adhesion molecule expression by the neutro phil, Specifically, hypertonicity induced shedding of L-selectin and p revented LPS-stimulated expression and activation of CD11b, both of wh ich might contribute to reduced sequestration in the lung. Impaired up -regulation of lung ICAM-1 may have also participated, although ex viv o studies suggest that alterations in neutrophils were sufficient to a ccount for the effect. Lung cytokine-induced neutrophil chemoattractan t did not differ between animals resuscitated with hypertonic saline v s Ringer's lactate. Considered together, these studies demonstrate a p ossible novel approach to inhibiting organ injury in disease processes characterized by neutrophil-mediated damage.