A dose-response study of graded reoxygenation on the carotid haemodynamics, matrix metalloproteinase-2 activities and amino acid concentrations in the brain of asphyxiated newborn piglets.
OBJECTIVE
It is controversial to choose an appropriate oxygen concentration to resuscitate asphyxiated newborns regarding the clinical and biochemical oxidative effects. We examined the vasomotor response to reoxygenation with graded reoxygenation and the effects on matrix metalloproteinases and amino acids of the immature brain.


METHODS
Thirty-two piglets (1-3 days, 1.5-2.1 kg) were instrumented for continuous monitoring of left common carotid and pulmonary arterial flows (Transonic). Piglets were randomized to a sham-operated control group (without hypoxia/reoxygenation) or 2 h hypoxia induced by decreasing the inspired oxygen concentration to 10-15%, followed by reoxygenation with 21, 50 or 100% oxygen for 1 h and then 21% oxygen for 3 h (n=8 each). The brains were then flash frozen and analyzed for matrix metalloproteinases and amino acid levels by zymography and HPLC, respectively.


RESULTS
After 2 h oxygen deprivation, the absolute carotid flow remained similar but accounted for 38% of cardiac output (increased from 17% at baseline, p=0.001). During early reoxygenation, the flow rose in the piglets resuscitated with air (p<0.05), but not in those with supplemental oxygen. Carotid vascular resistance correlated significantly with the arterial partial pressure of oxygen (r=0.7). There was an oxygen-dependent increase in global cerebral activity of matrix metalloproteinase-2 with specific increases in the basal ganglia of all hypoxic-reoxygenated brains. There were no significant differences in glutamate and other amino acids in any brain regions.


CONCLUSIONS
Although using high oxygen concentration to resuscitate asphyxiated newborn piglets increased carotid vascular resistance and cerebral matrix metalloproteinase-2 activity, there is no detrimental effect observed in this acute model of hypoxia-reoxygenation.
Richards
Justin G
JG
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Todd
Kathryn G
KG
Emara
Marwan
M
Haase
Erika
E
Cooper
Sarah L
SL
Bigam
David L
DL
Cheung
Po-Yin
PY
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000503:physiopathology*; D002302:Cardiac Output; D002339:Carotid Arteries / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage*; D010313:Partial Pressure; D012151:Resuscitation / Q000379:methods*; D013552:Swine; D014655:Vascular Resistance / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen