Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep.
BACKGROUND
Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.


OBJECTIVE
To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.


METHODS
129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min.


RESULTS
High VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.


CONCLUSIONS
Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.
Hillman
Noah H
NH
Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, OH 45236, USA. Noah.Hillman@cchmc.org
Pillow
J Jane
JJ
Ball
Molly K
MK
Polglase
Graeme R
GR
Kallapur
Suhas G
SG
Jobe
Alan H
AH
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D006612:High-Frequency Ventilation / Q000009:adverse effects*; D055370:Lung Injury / Q000209:etiology* / Q000517:prevention & control* / Q000662:veterinary; D011295:Prenatal Care / Q000379:methods; D012756:Sheep; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents