Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury.
BACKGROUND
The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.


METHODS
Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.


RESULTS
LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups.


CONCLUSIONS
Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Samantha K
SK
Barton
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, 3168, Australia.
Timothy J M
TJ
Moss
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, 3168, Australia.
Stuart B
SB
Hooper
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Kelly J
KJ
Crossley
School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, 6009, Australia.
Andrew W
AW
Gill
Department of Neonatal Medicine, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, 2065, Australia.
Martin
M
Kluckow
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Valerie
V
Zahra
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Flora Y
FY
Wong
Department of Pediatrics, Medical University Graz, Auenbruggerplatz 30, Graz, Austria, 8036.
Gerhard
G
Pichler
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Robert
R
Galinsky
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, 3168, Australia.
Suzanne L
SL
Miller
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia.
Mary
M
Tolcos
The Ritchie Centre, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria, 3168, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, 3168, Australia.
Graeme R
GR
Polglase
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology* / Q000662:veterinary; D002821:Chorioamnionitis / Q000503:physiopathology* / Q000662:veterinary; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D055370:Lung Injury / Q000503:physiopathology* / Q000662:veterinary; D011247:Pregnancy; D047928:Premature Birth / Q000503:physiopathology* / Q000662:veterinary; D012121:Respiration, Artificial / Q000379:methods* / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D012757:Sheep Diseases / Q000503:physiopathology*
D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8