Early protective effect of hypothermia in newborn pigs after hyperoxic, but not after normoxic, reoxygenation.
Abstract Mild hypothermia can attenuate the development of brain damage after asphyxia. Supplemental oxygen during resuscitation increases generation of reactive oxygen species, compared to room air. It is unknown if supplemental oxygen affects hypothermic neuroprotection. We studied the early effects of hyperoxic reoxygenation and subsequent hypothermia on tissue oxygenation, microcirculation, inflammation and brain damage after global hypoxia. Anesthetized newborn pigs were randomized to control (n=6), or severe global hypoxia (n=46). Three pigs died during hypoxia or reoxygenation. After 20-min reoxygenation with room air (n=22) or 100% oxygen (n=21), pigs were randomized to normothermia (deep rectal temperature 39 degrees C, n=22) or total body cooling (35 degrees C, n=21) for 6.5 h before the experiment was terminated. We demonstrated a differential effect of post-hypoxic hypothermia between animals reoxygenated with 100% oxygen and with room air, with reduced damage only in hypothermic animals reoxygenated with 100% oxygen (P=0.001). Hyperoxic reoxygenation resulted in a significant overshoot in striatal oxygen tension, without affecting microcirculation. Inflammatory response after the insult did not differ between groups. The results indicate an early protective effect of hypothermia which may vary with oxygen level used during reoxygenation.
Dalen
Marit L
ML
Department of Paediatric Research, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. marit.dalen@rr-research.no
Alme
Tomas N
TN
Munkeby
Berit H
BH
Løberg
Else Marit
EM
Pripp
Are Hugo
AH
Mollnes
Tom Eirik
TE
Rootwelt
Terje
T
Saugstad
Ola Didrik
OD
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000379:methods*; D007231:Infant, Newborn; D007249:Inflammation / Q000209:etiology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D016133:Polymerase Chain Reaction; D012151:Resuscitation / Q000009:adverse effects / Q000379:methods; D034421:Sus scrofa
D016207:Cytokines; D017931:DNA Primers; D010100:Oxygen