Regulation of cytochrome oxidase redox state during umbilical cord occlusion in preterm fetal sheep.
The preterm fetus is capable of surviving prolonged periods of severe hypoxia without neural injury for much longer than at term. To evaluate the hypothesis that regulated suppression of brain metabolism contributes to this remarkable tolerance, we assessed changes in the redox state of cytochrome oxidase (CytOx) relative to cerebral heat production, and cytotoxic edema measured using cerebral impedance, during 25 min of complete umbilical cord occlusion or sham occlusion in fetal sheep at 0.7 gestation. Occlusion was followed by rapid, profound reduction in relative cerebral oxygenation and EEG intensity and an immediate increase in oxidized CytOx, indicating a reduction in electron flow down the mitochondrial electron transfer chain. Confirming rapid suppression of cerebral metabolism there was a loss of the temperature difference between parietal cortex and body at a time when carotid blood flow was maintained at control values. As occlusion continued, severe hypotension/hypoperfusion developed, with a further increase in CytOx levels to a plateau between 8 and 13 min and a progressive rise in cerebral impedance. In conclusion, these data strongly suggest active regulation of cerebral metabolism during the initial response to severe hypoxia, which may help to protect the immature brain from injury.
Bennet
Laura
L
Department of Physiology, The University of Auckland, Private Bag 92019, Auckland, New Zealand. l.bennet@auckland.ac.nz
Roelfsema
Vincent
V
Dean
Justin M
JM
Wassink
Guido
G
Power
Gordon G
GG
Jensen
Ellen C
EC
Gunn
Alistair Jan
AJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002339:Carotid Arteries / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply; D004487:Edema; D017097:Electric Impedance; D004569:Electroencephalography; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005865:Gestational Age; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012756:Sheep / Q000196:embryology; D022722:Thermogenesis; D013997:Time Factors; D014470:Umbilical Cord / Q000503:physiopathology*
D001786:Blood Glucose; D002245:Carbon Dioxide; D019344:Lactic Acid; D003576:Electron Transport Complex IV; D010100:Oxygen