title: Amplified inflammatory response to sequential hemorrhage, resuscitation, and pulmonary fat embolism: an animal study.
abstract: BACKGROUND
  The objective of this study was to assess the role of pulmonary fat embolism caused by intramedullary pressurization of the femoral canal in the development of acute lung injury in the setting of acute hemorrhagic shock and resuscitation.
  
  
  METHODS
  Thirty New Zealand White rabbits were randomly assigned to one of four groups: (1) nine animals in which hemorrhagic shock was induced by carotid bleeding, resuscitation was performed, and the femoral canal was reamed and pressurized with bone cement to induce fat embolism (hemorrhagic shock and resuscitation/fat embolism [HR/FE] group); (2) six animals in which shock was induced by carotid bleeding, resuscitation was performed, and a sham knee incision was made and closed without drilling, reaming, or pressurization (hemorrhagic shock and resuscitation [HR] group); (3) eight animals in which no hemorrhage or shock was induced but the femoral canal was reamed and pressurized with bone cement to induce fat embolism (fat embolism [FE] group); and (4) seven animals that had a three-hour ventilation period followed by a sham knee incision (control group). The animals were ventilated for four hours following closure. Flow cytometry with use of antibodies against CD45 and CD11b was performed to test neutrophil activation in whole blood. Histological examination of lung specimens was also performed. Plasma and bronchoalveolar lavage fluid were analyzed for monocyte chemotactic peptide-1 and interleukin-8 levels with use of the ELISA (enzyme-linked immunosorbent assay) method.
  
  
  RESULTS
  Three animals in the HR/FE group died immediately after canal pressurization and were excluded. CD11b mean channel fluorescence was significantly elevated, as compared with baseline, only in the HR/FE group at two hours (p = 0.025) and four hours (p = 0.024) after knee closure. Histological analysis showed that only the HR/FE (p < 0.001) and HR (p = 0.010) groups had significantly greater infiltration of alveoli by polymorphonuclear leukocytes as compared with that in the controls. No significant differences in plasma cytokine levels were found between the groups. Only the HR/FE group had significantly higher interleukin-8 (p = 0.020) and monocyte chemotactic peptide-1 (p = 0.004) levels in the bronchoalveolar lavage fluid as compared with those in the controls.
  
  
  CONCLUSIONS
  Fat embolism from canal pressurization alone did not activate a pulmonary inflammatory response. The combination of hemorrhagic shock, resuscitation, and fat embolism elicited neutrophil activation, infiltration of alveoli by polymorphonuclear leukocytes, and inflammatory cytokine expression in bronchoalveolar lavage fluid.
authors.affiliation: St. Michael's Hospital, 55 Queen Street East, Suite 800, Toronto, M5C 1R6 ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Blankstein
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Byrick
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakane
authors.forename: K W Annie
authors.initials: KW
authors.lastname: Bang
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: Robin R
authors.initials: RR
authors.lastname: Richards
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.forename: Rad
authors.initials: R
authors.lastname: Zdero
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Emil H
authors.initials: EH
authors.lastname: Schemitsch
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004620:Embolism, Fat / Q000150:complications / Q000503:physiopathology*; D008297:Male; D011655:Pulmonary Embolism / Q000150:complications / Q000503:physiopathology*; D011817:Rabbits; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000503:physiopathology*