Hypertonic saline resuscitation attenuates neutrophil lung sequestration and transmigration by diminishing leukocyte-endothelial interactions in a two-hit model of hemorrhagic shock and infection.
BACKGROUND
Hypertonic saline (HTS) attenuates polymorphonuclear neutrophil (PMN)-mediated tissue injury after hemorrhagic shock. We hypothesized that HTS resuscitation reduces early in vivo endothelial cell (EC)-PMN interactions and late lung PMN sequestration in a two-hit model of hemorrhagic shock followed by mimicked infection.


METHODS
Thirty-two mice were hemorrhaged (40 mm Hg) for 60 minutes and then given intratracheal lipopolysaccharide (10 microg) 1 hour after resuscitation with shed blood and either HTS (4 mL/kg 7.5% NaCl) or Ringer's lactate (RL) (twice shed blood volume). Eleven controls were not manipulated. Cremaster intravital microscopy quantified 5-hour EC-PMN adherence, myeloperoxidase assay assessed lung PMN content (2 1/2 and 24 hours), and lung histology determined 24-hour PMN transmigration.


RESULTS
Compared with RL, HTS animals displayed 55% less 5-hour EC-PMN adherence (p = 0.01), 61% lower 24-hour lung myeloperoxidase ( p= 0.007), and 57% lower mean 24-hour lung histologic score ( p= 0.027).


CONCLUSIONS
Compared with RL, HTS resuscitation attenuates early EC-PMN adhesion and late lung PMN accumulation in hemorrhagic shock followed by inflammation. HTS resuscitation may attenuate PMN-mediated organ damage.
Pascual
José L
JL
Division of General Surgery, McGill University Health Center, Montréal, Québec, Canada.
Khwaja
Kosar A
KA
Ferri
Lorenzo E
LE
Giannias
Betty
B
Evans
David C
DC
Razek
Tarek
T
Michel
René P
RP
Christou
Nicolas V
NV
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D004926:Escherichia coli; D005440:Fluid Therapy / Q000379:methods*; D007249:Inflammation; D007552:Isotonic Solutions / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009195:Peroxidase / Q000032:analysis; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000494:pharmacology / Q000627:therapeutic use*; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D016037:Single-Blind Method; D013997:Time Factors
D007552:Isotonic Solutions; D008070:Lipopolysaccharides; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; D009195:Peroxidase