title: Amplified cytokine response and lung injury by sequential hemorrhagic shock and abdominal compartment syndrome in a laboratory model of ischemia-reperfusion.
abstract: BACKGROUND
  Increased intra-abdominal pressure has been shown to result in a myriad of physiologic aberrations that result in the abdominal compartment syndrome (ACS). The clinically relevant combination of hemorrhagic shock and resuscitation and subsequent ACS, however, has not been studied in detail. We hypothesized that sequential hemorrhagic shock (HS) and ACS would result in greater cytokine activation and polymorphonuclear neutrophil (PMN)-mediated lung injury than with either insult alone.
  
  
  METHODS
  Twenty Yorkshire swine (20-30 kg) were studied. Group 1 (n = 5) was hemorrhaged to a mean arterial pressure of 25 to 30 mm Hg for 60 minutes and resuscitated to baseline mean arterial pressure. Intra-abdominal pressure was then increased to 30 mm Hg above baseline and maintained for 60 minutes. Group 2 (n = 5) was subjected to HS alone and Group 3 (n = 5) to ACS alone. Group 4 (n = 5) had sham experiment without HS or ACS. Central and portal venous interleukin-1beta, interleukin-8, and tumor necrosis factor-alpha levels were serially measured. Bronchoalveolar lavage (BAL) for protein and PMNs was performed at baseline and 24 hours after resuscitation. Lung myeloperoxidase was evaluated at 24 hours after resuscitation.
  
  
  RESULTS
  Portal and central vein cytokine levels were equivalent but were significantly higher in Group 1 than in other groups. BAL PMNs were higher (p < 0.05) in Group 1 (4.1 +/- 2.0 x 106) than in the other groups (0.6 +/- 0.5, 1.4 +/- 1.3, and 0.1 +/- 0.0 x 106, respectively) and lung myeloperoxidase activity was higher (p < 0.05) in Group 1 (134.6 +/- 57.6 x 106/g) than in the other groups (40.3 +/- 14.7, 46.1 +/- 22.4, and 7.73 +/- 4.4 x 106/g, respectively). BAL protein was higher (p < 0.01) in Group 1 (0.92 +/- 0.32 mg/mL) compared with the other groups (0.22 +/- 0.08, 0.29 +/- 0.11, and 0.08 +/- 0.06 mg/mL, respectively).
  
  
  CONCLUSIONS
  In this clinically relevant model, sequential insults of ischemia-reperfusion (HS and resuscitation) and ACS were associated with significantly increased portal and central venous cytokine levels and more severe lung injury than HS or ACS alone.
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Medical College of Virginia Hospital, Richmond, Virginia, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Oda
authors.forename: Rao R
authors.initials: RR
authors.lastname: Ivatury
authors.forename: Charles R
authors.initials: CR
authors.lastname: Blocher
authors.forename: Ajai J
authors.initials: AJ
authors.lastname: Malhotra
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Sugerman
mesh_terms: D000007:Abdominal Injuries / Q000276:immunology*; D000818:Animals; D003161:Compartment Syndromes / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D005753:Gastric Mucosa / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008168:Lung / Q000276:immunology; D055370:Lung Injury; D023421:Models, Animal; D009504:Neutrophils / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology*; D012771:Shock, Hemorrhagic / Q000276:immunology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha