title: Superimposed gastric aspiration increases the severity of inflammation and permeability injury in a rat model of lung contusion.
abstract: BACKGROUND
  Lung contusion (LC) from blunt thoracic trauma is a clinically-prevalent condition that can progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Patients with LC are at risk for gastric aspiration at the time of trauma, but the combined insults have not been well-studied in animal models. This study tests the hypothesis that concurrent gastric aspiration (combined acid and small gastric particles, CASP) at the time of trauma significantly increases permeability injury and inflammation compared with LC alone, and also modifies the inflammatory response to include distinct features compared with the aspiration component of injury.
  
  
  METHODS
  Four groups of adult male Long-Evans rats were studied (LC, CASP, LC+CASP, uninjured controls). LC was induced in anesthetized rats at a fixed impact energy of 2.0 J, and CASP (1.2 mL/kg body weight, 40 mg particles/mL, pH=1.25) was instilled through an endotracheal tube. Lung injury and inflammation were assessed by arterial blood gases and levels of albumin, cells, and cytokines/chemokines in bronchoalveolar lavage (BAL) at 5 and 24 h.
  
  
  RESULTS
  Rats with LC+CASP had lower mean PaO(2)/FiO(2) ratios compared with LC alone at 24 h, and higher BAL albumin concentrations compared with either LC or CASP alone. Rats with LC+CASP versus LC had more severe inflammation based on higher levels of PMN in BAL at 5 h, increased whole lung myeloperoxidase (MPO) activity at 5 and 24 h, and increased levels of inflammatory mediators in BAL (TNFalpha, IL-1beta, and MCP-1 at 5 and 24 h; IL-10, MIP-2, and CINC-1 at 5 h). Rats with LC+CASP also had distinct aspects of inflammation compared with CASP alone, i.e., significantly higher levels of IL-10 (5 and 24 h), IL-1beta (24 h), CINC-1 (24 h), and MCP-1 (24 h), and significantly lower levels of MPO (5 h), MIP-2 (5 h), and CINC-1 (5 h).
  
  
  CONCLUSIONS
  Concurrent gastric aspiration can exacerbate permeability lung injury and inflammation associated with LC, and also generates a modified inflammatory response compared with aspiration alone. Unwitnessed gastric aspiration has the potential to contribute to more severe forms of LC injury associated with progression to ALI/ARDS and pneumonia in patients with thoracic trauma.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA. kraghave@umich.edu
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavendran
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: John C
authors.initials: JC
authors.lastname: Huebschmann
authors.forename: Jadwiga D
authors.initials: JD
authors.lastname: Helinski
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hutson
authors.forename: Merril T
authors.initials: MT
authors.lastname: Dayton
authors.forename: Robert H
authors.initials: RH
authors.lastname: Notter
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D055371:Acute Lung Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D002463:Cell Membrane Permeability; D003288:Contusions / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D053120:Respiratory Aspiration / Q000150:complications*; D015656:Respiratory Mechanics / Q000502:physiology; D012720:Severity of Illness Index
chemical_list: D000418:Albumins; D016207:Cytokines; D009195:Peroxidase; D010100:Oxygen