Persistent neurochemical changes in neonatal piglets after hypoxia-ischemia and resuscitation with 100%, 21% or 18% oxygen.
BACKGROUND
Neonatal hypoxia-ischemia (HI) is a common complication of pregnancy and delivery. Conventional clinical practice is to resuscitate neonates with 100% O2, and evidence is building to suggest resuscitation with lower O2 concentrations is safer. Significant neurochemical changes are associated with HI injury and persistent changes in amino acids are related to cell death, therefore we used a swine survival model of neonatal HI-reoxygenation (HI/R) to investigate the effects of resuscitation with 100%, 21% or 18% O2 on amino acid neurotransmitters.


METHODS
In a blinded randomized fashion, following permanent ligation of the left common carotid artery, newborn pigs (1-4 d, 1.7-2.5 kg) received alveolar normocapnic hypoxia (FiO2=0.15, 2h) and were reoxygenated with 18%, 21% or 100% O2. After a 4-day survival period, brain regions were processed for amino acid levels using high-performance liquid chromatography (HPLC).


RESULTS
Results showed that resuscitation with different O2 concentrations caused hemispheric and regional changes in all amino acids investigated including glutamate, alanine, gamma-amino butyric acid, glycine and aspartate, 4 days post-HI. Resuscitation with 100% O2 significantly increased glutamate and glycine in the dorsal cortex contralateral to the ligated common carotid artery, compared to piglets resuscitated with 21% O2. Additionally, piglets resuscitated with 21% O2 had significantly lower alanine levels than those resuscitated with 18% O2.


CONCLUSIONS
Significant resuscitation-dependent changes in amino acid neurotransmitters are still evident 4 days post-HI in the newborn piglet. These data suggest that persistent changes in neurochemistry occur 4 days after HI/R and further studies are warranted to elucidate the consequences of this on neonatal brain development.
Jantzie
Lauren L
LL
Neurochemical Research Unit, Department of Psychiatry, 1E7 Walter Mackenzie Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2R7.
Cheung
Po-Yin
PY
Obaid
Laila
L
Emara
Marwan
M
Johnson
Scott T
ST
Bigam
David L
DL
Todd
Kathryn G
KG
D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002851:Chromatography, High Pressure Liquid; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000628:therapy*; D010102:Oxygen Inhalation Therapy; D012151:Resuscitation / Q000379:methods*; D013552:Swine
D000596:Amino Acids