Methylprednisolone fails to preserve pulmonary surfactant and blood-air barrier integrity in a porcine cardiopulmonary bypass model.
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.
Mühlfeld
Christian
C
Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany. muehlfeld@ana.unibe.ch
Liakopoulos
Oliver J
OJ
Schaefer
Inga-Marie
IM
Schöndube
Friedrich A
FA
Richter
Joachim
J
Dörge
Hilmar
H
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
D000893:Anti-Inflammatory Agents; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone