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Updated: Aug 26, 2026
Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory
Jeffrey M Pearl1, Steven M Schwartz, David P Nelson
1Department of Cardiology, Cincinnati Children's Hospital Medical Center, OH, USA. jeffrey.pearl@cchmc.org
Insights
Glucocorticoids, specifically methylprednisolone, prevent pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. This protective effect is linked to reduced endothelin-1 and nuclear factor-kappaB activation.
Area of Science:
- Cardiovascular Surgery
- Pediatric Cardiology
- Pharmacology
Background:
- Glucocorticoids are routinely used in pediatric patients undergoing congenital heart defect repair with cardiopulmonary bypass.
- The precise mechanisms by which glucocorticoids improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest remain incompletely understood.
Purpose of the Study:
- To investigate the hypothesis that glucocorticoids can enhance cardiopulmonary recovery following cardiopulmonary bypass and deep hypothermic circulatory arrest.
- To elucidate the underlying mechanisms of glucocorticoid action in this context.
Main Methods:
- Crossbred piglets underwent deep hypothermic circulatory arrest (120 minutes) during cardiopulmonary bypass.
- Methylprednisolone was administered either intraoperatively or preoperatively and intraoperatively.
- Control animals received saline without glucocorticoids.
Main Results:
- Preoperative and intraoperative glucocorticoid administration prevented the increase in pulmonary vascular resistance observed in controls.
- Glucocorticoid treatment significantly reduced plasma endothelin-1 levels post-procedure.
- Reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity were noted in glucocorticoid-treated groups.
- Increased inhibitor kappaBalpha levels indicated nuclear factor-kappaB pathway inhibition.
Conclusions:
- Glucocorticoids effectively prevent pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.
- Reduced endothelin-1, intercellular adhesion molecule-1, and myeloperoxidase activity contribute to the protective effects of glucocorticoids.
- Inhibition of nuclear factor-kappaB and decreased neutrophil activation are key mechanisms underlying glucocorticoid-induced cardiopulmonary protection.
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.
