Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs

Graeme Polglase, Samantha Kate Barton, Jacqueline Melville, Valerie Anne Zahra, Megan Jane Wallace, Melissa Li-Lian Siew, Mary Tolcos, Timothy James Murugesan Moss

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Ventilation-induced lung injury (VILI) of preterm neonates likely 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. Methods: Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 minutes to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU/kg: 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. Results: Vent+EPO lambs received higher FiO2, PaO2 and oxygenation during the first 10 minutes 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 compared to 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. Conclusions: Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO is used for lung protection in preterm infants.
Original languageEnglish
Pages (from-to)1993 - 2002
Number of pages10
JournalThe Journal of Physiology
Volume592
Issue number9
DOIs
Publication statusPublished - 2014

Cite this

Polglase, Graeme ; Barton, Samantha Kate ; Melville, Jacqueline ; Zahra, Valerie Anne ; Wallace, Megan Jane ; Siew, Melissa Li-Lian ; Tolcos, Mary ; Moss, Timothy James Murugesan. / Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs. In: The Journal of Physiology. 2014 ; Vol. 592, No. 9. pp. 1993 - 2002.
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title = "Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs",
abstract = "Ventilation-induced lung injury (VILI) of preterm neonates likely 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. Methods: Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 minutes to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU/kg: 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. Results: Vent+EPO lambs received higher FiO2, PaO2 and oxygenation during the first 10 minutes 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 compared to 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. Conclusions: Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO is used for lung protection in preterm infants.",
author = "Graeme Polglase and Barton, {Samantha Kate} and Jacqueline Melville and Zahra, {Valerie Anne} and Wallace, {Megan Jane} and Siew, {Melissa Li-Lian} and Mary Tolcos and Moss, {Timothy James Murugesan}",
year = "2014",
doi = "10.1113/jphysiol.2013.270348",
language = "English",
volume = "592",
pages = "1993 -- 2002",
journal = "The Journal of Physiology",
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Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs. / Polglase, Graeme; Barton, Samantha Kate; Melville, Jacqueline; Zahra, Valerie Anne; Wallace, Megan Jane; Siew, Melissa Li-Lian; Tolcos, Mary; Moss, Timothy James Murugesan.

In: The Journal of Physiology, Vol. 592, No. 9, 2014, p. 1993 - 2002.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs

AU - Polglase, Graeme

AU - Barton, Samantha Kate

AU - Melville, Jacqueline

AU - Zahra, Valerie Anne

AU - Wallace, Megan Jane

AU - Siew, Melissa Li-Lian

AU - Tolcos, Mary

AU - Moss, Timothy James Murugesan

PY - 2014

Y1 - 2014

N2 - Ventilation-induced lung injury (VILI) of preterm neonates likely 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. Methods: Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 minutes to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU/kg: 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. Results: Vent+EPO lambs received higher FiO2, PaO2 and oxygenation during the first 10 minutes 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 compared to 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. Conclusions: Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO is used for lung protection in preterm infants.

AB - Ventilation-induced lung injury (VILI) of preterm neonates likely 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. Methods: Lambs at 126 days of gestation (term is 147 days) were delivered and ventilated with a high tidal volume strategy for 15 minutes to cause lung injury, then received gentle ventilation until 2 h of age. Lambs were randomized to receive intravenous EPO (5000 IU/kg: 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. Results: Vent+EPO lambs received higher FiO2, PaO2 and oxygenation during the first 10 minutes 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 compared to 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. Conclusions: Prophylactic EPO exacerbates VILI, which may increase the incidence and severity of long-term respiratory disease. More studies are required before EPO is used for lung protection in preterm infants.

UR - http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2013.270348/pdf

U2 - 10.1113/jphysiol.2013.270348

DO - 10.1113/jphysiol.2013.270348

M3 - Article

VL - 592

SP - 1993

EP - 2002

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 9

ER -