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Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs
Graeme R Polglase1, Samantha K Barton, Jacqueline M Melville
1Ritchie Centre, Monash Institute of Medical Research, PO Box 5418, Clayton, Victoria, 3168, Australia. graeme.polglase@monash.edu.
Insights
Prophylactic erythropoietin (EPO) administration did not reduce ventilation-induced lung injury (VILI) in preterm lambs. Instead, EPO worsened lung inflammation and injury, suggesting it may increase the risk of bronchopulmonary dysplasia (BPD).
Area of Science:
- Neonatal physiology
- Pulmonology
- Pharmacology
Background:
- Ventilation-induced lung injury (VILI) is a significant concern in preterm neonates and may contribute to bronchopulmonary dysplasia (BPD).
- Erythropoietin (EPO) has been investigated as a potential therapeutic agent for BPD, but its effects on VILI are not well understood.
Purpose of the Study:
- To investigate the prophylactic effects of erythropoietin (EPO) on ventilation-induced lung injury (VILI) in preterm newborn lambs.
- To assess whether EPO administration influences lung inflammation, injury markers, and systemic acute phase response in the context of VILI.
Main Methods:
- Preterm lambs (126 days gestation) were subjected to a high tidal volume ventilation strategy to induce lung injury, followed by gentle ventilation.
- Lambs were randomized to receive either intravenous EPO (5000 IU/kg) or a placebo (phosphate-buffered saline) shortly after birth.
- Lung tissue was analyzed for histological and molecular markers of inflammation and injury, and liver samples assessed the systemic acute phase response.
Main Results:
- While EPO-treated lambs showed transiently higher oxygenation, they exhibited significantly increased total lung injury scores, airway wall thickness, inflammation, and hemorrhage compared to placebo-treated lambs.
- Ventilated lambs, regardless of EPO treatment, showed elevated lung inflammation and markers of lung and systemic injury compared to unventilated controls.
- EPO administration exacerbated lung inflammation and markers of both lung and systemic injury.
Conclusions:
- Prophylactic erythropoietin administration exacerbates ventilation-induced lung injury in preterm lambs.
- These findings suggest that EPO may potentially increase the incidence and severity of long-term respiratory complications like bronchopulmonary dysplasia.
- Further research is warranted to evaluate the safety and efficacy of EPO for lung protection in preterm infants.
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.
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