Immunomodulatory Effects Of HSH Resuscitation On The Development Of Lung Inflammation Fol Lowing Hemorrhagic Shock

Objective : To investigation the molecular mechanisms underlying the immunomodulatory effects of hypertonic sodium chloride and hetastarch 40 injection (HSH) resuscitation on the development of lung inflammation in a hemorrhagic shock model.Methods : Sprague-Dawley rats were subjected to hemorrhagic shock and intratracheal LPS , the so-called two hit rodent model .The animals which were resuscitated by transfusion of the shed blood and either in equivalent amount of Ringer's lactate (RL) or a 6ml/kg volume of hypertonic sodium chloride and hetastarch injection 40 were sacrificed at 1 , 2 , 4 hour after rescucitation , respectively . Blood sample was collected into 75u of heparin/ml to prevent clotting . Surface expression of adhesion molecule CD11b on circulating polymorphonuclear (PMN) was measured by flow cytometry . Lung tissue myeloperoxidase enzyme (MPO) activities reflecting total lung neutrophil infiltration was assessed by modified Bradly's method using H2O2 as a substrate . Bronchoalveolar lavage fluid nuetrophil counts , protein measurements , lung ratio of wet to dryness , and the degree of histopathologic injury were determined.Results : Resuscitation with hypertonic sodium chloride and hetastarch injection 40 significantly reduced bronchoalverlar lavage fluid neutrophil counts , albumin leak , lung edema , and the dgree of histopathologic injure compared with resuscitation with Ringer's lactate at various experimental timepoints ,respectively ( P<0.01 ). The expression of CDllb on PMNs in RL group was higher than that in HSH group(P<0.01).This beneficial effect of hypertonic sodium chloride and hetastarch 40 injection may be related to altrerd adhesion molecule expression by the neutrophil.Conclusion : Hypertonic sodium chloride and hetastarch 40 injection resuscitation attenuated lung neutrophil sequestration and lung inflammation after hemorrhagic shock and LPS by abolishing adhesion molecule CDllb up-regulation . These studies demonstrate a possible novel approach to inhibiting organ injury in hemorrhagic shock processes characterized by neutrophil-mediated damage.