title: Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation-induced pulmonary inflammation through attenuation of neutrophil degranulation and proinflammatory mediator synthesis.
abstract: BACKGROUND
  Ringer's lactate (RL), the current standard resuscitation fluid, potentiates neutrophil activation and is associated with pulmonary inflammation. Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to attenuate hemorrhagic shock-induced injury when compared with RL. Because the neutrophil plays a major role in postshock inflammation, we hypothesized that HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL.
  
  
  METHODS
  Sprague-Dawley rats underwent controlled shock and were resuscitated with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg). Animals who did not undergo shock or resuscitation served as controls. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme-linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and immunohistochemistry.
  
  
  RESULTS
  HSPTX resuscitation led to a 62% decrease in CINC levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11% with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p < 0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway epithelial cells.
  
  
  CONCLUSIONS
  Collectively, the attenuation of pulmonary inflammation with HSPTX after shock when compared with RL is associated with downregulation of neutrophil activation, oxidative stress, and proinflammatory mediator production.
authors.affiliation: Division of Trauma and Surgical Critical Care, Department of Surgery, University of California School of Medicine, San Diego, CA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Deree
authors.forename: Joilson O
authors.initials: JO
authors.lastname: Martins
authors.forename: Alex
authors.initials: A
authors.lastname: Leedom
authors.forename: Brian
authors.initials: B
authors.lastname: Lamon
authors.forename: James
authors.initials: J
authors.lastname: Putnam
authors.forename: Tercio
authors.initials: T
authors.lastname: de Campos
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: Paul
authors.initials: P
authors.lastname: Wolf
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015550:Cell Degranulation; D004797:Enzyme-Linked Immunosorbent Assay; D005440:Fluid Therapy / Q000009:adverse effects* / Q000379:methods; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000628:therapy*
chemical_list: D018836:Inflammation Mediators; D018945:Monocyte Chemoattractant Proteins; D012462:Saline Solution, Hypertonic; D051547:Heme Oxygenase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010431:Pentoxifylline