title: Methylprednisolone fails to preserve pulmonary surfactant and blood-air barrier integrity in a porcine cardiopulmonary bypass model.
abstract: BACKGROUND
  Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model.
  
  
  METHODS
  After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology).
  
  
  RESULTS
  Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO2 and PaO2/FiO2 were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05).
  
  
  CONCLUSIONS
  Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.
authors.affiliation: Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany. muehlfeld@ana.unibe.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Liakopoulos
authors.forename: Inga-Marie
authors.initials: IM
authors.lastname: Schaefer
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Schöndube
authors.forename: Joachim
authors.initials: J
authors.lastname: Richter
authors.forename: Hilmar
authors.initials: H
authors.lastname: Dörge
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001706:Biopsy; D015824:Blood-Air Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008775:Methylprednisolone / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011897:Random Allocation; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone