title: Cross-transfusion of postshock mesenteric lymph provokes acute lung injury.
abstract: OBJECTIVE
  Substantial investigation has implicated mesenteric lymph as the mechanistic link between gut ischemia/reperfusion (I/R) and distant organ injury. Specifically, lymph diversion prevents acute lung injury (ALI) in vitro, and bioactive lipids and proteins isolated from postshock mesenteric lymph (PSML) maintain bioactivity in vitro. However, Koch's postulates remain to be satisfied via direct cross-transfusion into a naïve animal. We therefore hypothesized that real time cross-transfusion of postshock mesenteric lymph provokes acute lung injury.
  
  
  METHODS
  One set of Sprague-Dawley rats (lymph donors) was anesthetized, with the mesenteric lymph ducts cannulated and exteriorized to drain freely into a siliconates plastic cup; concurrently, a second group of rats ( lymph recipients) was anesthetized, with a cannula inserted into the animal's right internal jugular vein. Blood was removed from the donor rats to induce hemorrhagic shock (MAP of 35 mmHg × 45 min). The recipient rats were positioned 10 cm below the plastic cup, which emptied into the jugular vein cannula. Thus, mesenteric lymph from the shocked donor rat was delivered to the recipient rat at the rate generated during shock and the subsequent 3 h of resuscitation.
  
  
  RESULTS
  Neutrophil (PMN) accumulation in the lungs was substantially elevated in the postshock lymph cross-transfusion group compared to both sham lymph cross-transfusion and instrumented control (MPO: 9.42 ± 1.55 versus 2.81 ± 0.82 U/mg lung tissue in postshock versus sham lymph cross-transfusion, n = 6 in each group, P = 0.02). Additionally, cross-transfusion of PSML induced oxidative stress in the lung (0.21 ± 0.03 versus 0.10 ± 0.01 micromoles MDA per mg lung tissue in lymph cross-transfusion versus instrumented control, n = 6 in each group, P = 0.046). Furthermore, transfusion of PSML provoked lung injury (BAL protein 0.77 ± 0.18 versus 0.15 ± 0.02 mg/mL protein in BALF, postshock versus sham lymph cross-transfusion, n = 6 in each group, P = 0.004).
  
  
  CONCLUSIONS
  Cross-transfusion of PSML into a naïve animal leads to PMN accumulation and provokes ALI. These data provide evidence that postshock agents released into mesenteric lymph are capable of provoking distant organ injury.
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colorado, USA.
authors.forename: Max Valentin
authors.initials: MV
authors.lastname: Wohlauer
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Harr
authors.forename: John
authors.initials: J
authors.lastname: Eun
authors.forename: Miguel
authors.initials: M
authors.lastname: Fragoso
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology; D000818:Animals; D019317:Evidence-Based Medicine; D015633:Extravascular Lung Water / Q000276:immunology; D008196:Lymph / Q000166:cytology* / Q000276:immunology*; D008643:Mesentery / Q000276:immunology; D009102:Multiple Organ Failure / Q000209:etiology / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000637:transplantation*; D018384:Oxidative Stress / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000276:immunology