The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep.
Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml(-1)) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia.
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Christopher A
CA
Lear
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Miriam E
ME
Koome
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Joanne O
JO
Davidson
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Paul P
PP
Drury
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Josine S
JS
Quaedackers
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Robert
R
Galinsky
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.
Alistair J
AJ
Gunn
Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand l.bennet@auckland.ac.nz.
Laura
L
Bennet
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058256:Brain Waves; D002560:Cerebrovascular Circulation; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption; D011247:Pregnancy; D012756:Sheep
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone