title: Improved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-kappa B activation after traumatic hemorrhage.
abstract: OBJECTIVE
  We hypothesized that modifying resuscitation would alter hemorrhagic shock-induced respiratory dysfunction and correlate with nuclear factor-kappa B and cytokine expression.
  
  
  METHODS
  Randomized, controlled, prospective study.
  
  
  METHODS
  University hospital trauma research laboratory.
  
  
  METHODS
  Female, Swiss Webster mice, 8-12 wks old.
  
  
  METHODS
  Hemorrhagic shock was induced by removing 0.025 mL of blood/g of body weight via a carotid catheter. Animals were resuscitated 30 mins later. Mice were randomized into four groups: group I was cannulated but not bled (sham); group II received normal saline to three times their shed blood volume; group III received their shed blood; and group IV received shed blood + normal saline at two times shed blood volume.
  
  
  RESULTS
  We measured the following: serum lactates at the end of shock and after resuscitation, pulmonary function before any instrumentation and after 24 hrs, cytokine concentrations by enzyme-linked immunosorbent assay, and nuclear factor-kappa B activity by electrophoretic mobility shift assay. Groups that were hemorrhaged had significant hypotension and a significant increase in serum lactates over 30 mins. Resuscitation returned the blood pressure to baseline in all groups, and lactates improved in all groups except group II. Group II also demonstrated a significant decrease in pulmonary function characterized by increased airway resistance and decreases in minute volume, lung compliance, and alveolar function. Bronchoalveolar fluid and serum interleukin-6 and whole lung nuclear factor-kappa B activity also were elevated significantly in group II.
  
  
  CONCLUSIONS
  Group II demonstrated the least improvement in serum lactate after resuscitation, the most significant acute lung injury, and the greatest interleukin-6 and nuclear factor-kappa B response. Group IV mice had the least acute lung injury, with no detectable interleukin-6 response. Improved resuscitation with crystalloid and shed blood minimized acute lung injury. The reduction in pulmonary dysfunction after improved resuscitation may be attributable to a blunting of the nuclear factor-kappa B and interleukin-6 responses to hemorrhage.
authors.affiliation: Trauma Research Laboratory, University of Virginia Health System, Department of Surgery, Charlottesville, VA 22908, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Claridge
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Schulman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Young
mesh_terms: D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis*; D019344:Lactic Acid / Q000097:blood; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D055370:Lung Injury; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D009195:Peroxidase / Q000378:metabolism; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000378:metabolism* / Q000401:mortality; D013223:Statistics as Topic; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D019344:Lactic Acid; D009195:Peroxidase