title: Mesenteric lymph is responsible for post-hemorrhagic shock systemic neutrophil priming.
abstract: BACKGROUND
  Hemorrhagic shock-induced splanchnic hypoperfusion has been implicated as a priming event in the two event model of multiple organ failure (MOF). We have previously shown that early postinjury neutrophil (PMN) priming identifies the injured patient at risk for MOF. Recent in vitro studies have demonstrated that postshock mesenteric lymph primes isolated human neutrophils. We hypothesize that lymphatic diversion before hemorrhagic shock abrogates systemic PMN priming and subsequent lung injury.
  
  
  METHODS
  Sprague-Dawley rats (n >or= 5 per group) underwent hemorrhagic shock (MAP 40 mm Hg x 30 min) and resuscitation (shed blood + 2x crystalloid) with and without mesenteric lymphatic duct diversion. Sham animals underwent anesthesia and laparotomy. Whole blood was taken 2 hours after resuscitation, heparinized, and incubated for 5 min at 37 degrees C. Surface expression of CD11b (a marker for PMN priming) was determined by flow-cytometry compared with isotype controls. In addition, lung myeloperoxidase (MPO) was measured for PMN sequestration, and Evans blue lung leak was assessed in the bronchoalveolar lavage fluid in sham, and shock +/- lymph diversion animals.
  
  
  RESULTS
  Hemorrhagic shock resulted in increased surface expression of PMN CD11b relative to sham (23.8 +/- 6.7 vs. 9.9 +/- 0.6). Mesenteric lymphatic diversion before hemorrhagic shock abrogated this effect (8.0 +/- 2.6). Lung PMN accumulation, as assessed by MPO, was greater in the lungs of nondiverted (113 +/- 14 MPO/mg lung) versus sham (55 +/- 4 MPO/mg lung, p < 0.05); lymph diversion reduced lung PMNs to control levels (71 +/- 6.5 MPO/mg lung, p < 0.05). Evans blue lung leak was 1.6 times sham in the hemorrhagic shock group; this was returned to sham levels after lymph diversion (p < 0.05).
  
  
  CONCLUSIONS
  Post-hemorrhagic shock mesenteric lymph primes circulating PMNs, promotes lung PMN accumulation, and provokes acute lung injury. Lymphatic diversion abrogates these pathologic events. These observations further implicate the central role of mesenteric lymph in hemorrhagic shock-induced lung injury. Characterizing the PMN priming agents could provide insight into the pathogenesis of postinjury MOF and ultimately new therapeutic strategies.
authors.affiliation: Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Gonzalez
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: D J
authors.initials: DJ
authors.lastname: Ciesla
authors.forename: W L
authors.initials: WL
authors.lastname: Biffl
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008168:Lung / Q000201:enzymology; D055370:Lung Injury; D008208:Lymphatic System / Q000601:surgery; D016177:Macrophage-1 Antigen / Q000097:blood*; D008297:Male; D008643:Mesentery; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications*
chemical_list: D016177:Macrophage-1 Antigen; D009195:Peroxidase