title: Postresuscitation tissue neutrophil infiltration is time-dependent and organ-specific.
abstract: BACKGROUND
  Hemorrhagic shock with conventional resuscitation (CR) primes circulating neutrophils and activates vascular endothelium for increased systemic inflammation, superoxide release, and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) with intraperitoneal instillation of a clinical peritoneal dialysis solution decreases systemic inflammation and edema formation by enhancing tissue perfusion. The aim of this study is to determine the effect of adjunctive DPR on neutrophil and fluid sequestration.
  
  
  METHODS
  Anesthetized rats were hemorrhaged to 40% mean arterial pressure for 60 min. Animals were randomized for CR with the return of the shed blood plus two volumes of saline, or CR plus adjunctive DPR with 30 mL of intraperitoneal injection of a clinical peritoneal dialysis solution. Tissue myeloperoxidase (MPO) level, a marker of neutrophil sequestration, and total water content were assessed in the gut, lung, and liver in sham animals and at time-points 1, 2, 4, and 24 h postresuscitation.
  
  
  RESULTS
  Resuscitation from hemorrhagic shock increases MPO level in all tissues in a near-linear fashion during the first 4 h following resuscitation. This occurs irrespective of the resuscitation regimen used. Tissue MPO level returned to baseline at 24 h following resuscitation except in the liver where CR and not adjunctive DPR caused a significant rebound increase. Adjunctive DPR prevented the CR-mediated obligatory fluid sequestration in the gut and lung and maintained a relative normal tissue water in these organs compared with CR alone (n = 7, F = 10.1, P < 0.01).
  
  
  CONCLUSIONS
  Hemorrhagic shock and resuscitation produces time-dependent organ-specific trends of neutrophil sequestration as measured with tissue levels of myeloperoxidase, a marker of neutrophil infiltration. Modulation of the splanchnic blood flow by direct peritoneal resuscitation did not alter the time-dependent neutrophil infiltration in end-organs, suggesting a subordinate role of blood rheology in the hemorrhage-induced neutrophil sequestration. Vulnerable window for neutrophil-mediated tissue damage exists during the first 4 h following resuscitation from hemorrhagic shock in rats. Direct peritoneal resuscitation prevents the early obligatory fluid sequestration and promotes early fluid mobilization.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40292, USA.
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: James E
authors.initials: JE
authors.lastname: Campbell
authors.forename: James C
authors.initials: JC
authors.lastname: Peyton
authors.forename: Richard N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005440:Fluid Therapy; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D009928:Organ Specificity / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D009195:Peroxidase