title: Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs.
abstract: Ventilation-induced lung injury (VILI) of preterm neonates probably contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Erythropoietin (EPO) has been suggested as a therapy for BPD. The aim of this study was to determine whether prophylactic administration of EPO reduces VILI in preterm newborn lambs. Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 min to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU kg(-1): Vent+EPO; n = 6) or phosphate-buffered saline (Vent; n = 7) soon after birth: unventilated controls (UVC; n = 8) did not receive ventilation or any treatment. Physiological parameters were recorded throughout the experimental procedure. Samples of lung were collected for histological and molecular assessment of inflammation and injury. Samples of liver were collected to assess the systemic acute phase response. Vent+EPO lambs received higher F IO 2, P aO 2 and oxygenation during the first 10 min than Vent lambs. There were no differences in physiological indices beyond this time. Total lung injury score, airway wall thickness, inflammation and haemorrhage were higher in Vent+EPO lambs than in Vent lambs. Lung inflammation and early markers of lung and systemic injury were elevated in ventilated lambs relative to unventilated lambs; EPO administration further increased lung inflammation and markers of lung and systemic injury. Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO can be used for lung protection in preterm infants.
authors.affiliation: Ritchie Centre, Monash Institute of Medical Research, PO Box 5418, Clayton, Victoria, 3168, Australia. graeme.polglase@monash.edu.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Barton
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Melville
authors.forename: Valerie
authors.initials: V
authors.lastname: Zahra
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Wallace
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Siew
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D055370:Lung Injury / Q000139:chemically induced* / Q000209:etiology* / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced* / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D011897:Random Allocation; D012121:Respiration, Artificial / Q000009:adverse effects*; D034561:Sheep, Domestic
chemical_list: D004921:Erythropoietin