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Ann Thorac Surg 2004;77:994-1000
© 2004 The Society of Thoracic Surgeons


Original article: cardiovascular

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest

Jeffrey M. Pearl, MDa,c*, Steven M. Schwartz, MDb, David P. Nelson, MD, PhDb,d, Connie J. Wagner, BSa, Jefferson M. Lyons, MDa,c, Steven M. Bauer, MSb, Jodie Y. Duffy, PhDa,b,d

a Department of Pediatric Cardiothoracic Surgery and Cincinnati, OH, USA
b Department of Cardiology, Cincinnati, OH, USA
c Department of Cincinnati Children's Hospital Medical Center; and Department of Surgery Cincinnati, OH, USA
d Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA

Accepted for publication September 8, 2003.

* Address reprint requests to Dr Pearl, Clinical Surgery, Pediatric Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, OSB3, Cincinnati, OH 45229, USA.
e-mail: jeffrey.pearl{at}cchmc.org

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest.

METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38°C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline.

RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 ± 40 to 364 ± 29 dynes · s/cm5 at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 ± 55 dynes · s/cm5 at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 ± 54 dynes · s/cm5). Plasma endothelin-1 in controls increased from 1.3 ± 0.2 at baseline to 9.9 ± 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 ± 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 ± 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor {kappa}B{alpha}, the inhibitor of nuclear factor-{kappa}B, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05).

CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-{kappa}B, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.

Abbreviations: CPB • cardiopulmonary bypass • DHCA • deep hypothermic circulatory arrest • FiO2 • fraction of inspired oxygen • GAPDH • glyceraldehyde-3-phosphate dehydrogenase • GC • glucocorticoids • ICAM-1 • intercellular adhesion molecule-1 • I{kappa}B • inhibitor kappa B • LV • left ventricle • NF-{kappa}B • nuclear factor-kappa B • NOS • nitric oxide synthase • PVR • pulmonary vascular resistance • PO2 • partial oxygen pressure • PCO2 • partial carbon dioxide pressure • RV • right ventricle




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