Methylprednisolone Fails to Preserve Pulmonary Surfactant and Blood–Air Barrier Integrity in a Porcine Cardiopulmonary Bypass Model

Mühlfeld, Christian; Liakopoulos, Oliver J.; Schaefer, Inga-Marie; Schöndube, Friedrich A.; Richter, Joachim; Dörge, Hilmar

doi:10.1016/j.jss.2007.03.026

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Volume 146, Issue 1 , Pages 57-65, 1 May 2008

Methylprednisolone Fails to Preserve Pulmonary Surfactant and Blood–Air Barrier Integrity in a Porcine Cardiopulmonary Bypass Model

Christian Mühlfeld, M.D.
- Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany
- Institute of Anatomy, Division of Histology, University of Bern, Bern, Switzerland
- These authors contributed equally to this work.
- To whom correspondence and reprint requests should be addressed at University of Berne, Institute of Anatomy, Division of Histology, Baltzerstrasse 2, CH-3000 Bern 9, Switzerland.
Oliver J. Liakopoulos, M.D.
- Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Göttingen, Germany
- These authors contributed equally to this work.
Inga-Marie Schaefer, B.M.
- Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany
Friedrich A. Schöndube, M.D.
- Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Göttingen, Germany
Joachim Richter, M.D.
- Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany
Hilmar Dörge, M.D.
- Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Göttingen, Germany

Received 18 January 2007 published online 22 June 2007.

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.

Materials and 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-α (TNF-α, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-α (Western blot) or blood–air barrier and surfactant morphology (electron microscopy, stereology).

Results

Systemic TNF-α 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-α 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).

Conclusion

Despite reduction of the systemic inflammatory response and pulmonary TNF-α generation, methylprednisolone fails to decrease pulmonary TNF-α and to preserve pulmonary surfactant morphology, blood–air barrier integrity, and pulmonary function after CPB.

Key Words: methylprednisolone, cardiopulmonary bypass, inflammation, stereology, electron microscopy, lung