Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest.
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 degrees 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/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) 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/cm(5)). 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 kappaBalpha, the inhibitor of nuclear factor-kappaB, 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-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.
Pearl
Jeffrey M
JM
Department of Cardiology, Cincinnati Children's Hospital Medical Center, OH, USA. jeffrey.pearl@cchmc.org
Schwartz
Steven M
SM
Nelson
David P
DP
Wagner
Connie J
CJ
Lyons
Jefferson M
JM
Bauer
Steven M
SM
Duffy
Jodie Y
JY
D000818:Animals; D002315:Cardiopulmonary Bypass; D015815:Cell Adhesion Molecules / Q000032:analysis; D019332:Endothelin-1 / Q000097:blood; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006324:Heart Arrest, Induced; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D007036:Hypothermia, Induced; D008168:Lung / Q000737:chemistry; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018375:Neutrophil Activation / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D011300:Preoperative Care; D011652:Pulmonary Circulation / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D015815:Cell Adhesion Molecules; D019332:Endothelin-1; D005938:Glucocorticoids; D016328:NF-kappa B; D009195:Peroxidase; D008775:Methylprednisolone