Exposure to hypoxic-ischaemia (HI) is consistently followed by a delayed fall in
cerebral perfusion. In preterm fetal sheep this is associated with impaired
cerebral oxygenation, consistent with mismatch between perfusion and metabolism.
In the present study we tested the hypothesis that alpha-adrenergic inhibition
after HI would improve cerebral perfusion, and so attenuate mismatch and reduce
neural injury. Chronically instrumented preterm (0.7 gestation) fetal sheep
received sham-HI (n = 10) or HI induced by complete umbilical cord occlusion for
25 minutes. From 15 minutes to 8 hours after HI, fetuses received either an
intravenous infusion of a non-selective alpha-adrenergic antagonist,
phentolamine (10 mg bolus, 10 mg/h infusion, n = 10), or saline (n = 10). Fetal
brains were processed for histology 72 hours post-HI. Phentolamine infusion was
associated with increased epileptiform transient activity and a greater fall in
cerebral oxygenation in the early post-HI recovery phase. Histologically,
phentolamine was associated with greater loss of oligodendrocytes and
hippocampal neurons. In summary, contrary to our hypothesis, alpha-adrenergic
inhibition increased epileptiform transient activity with an exaggerated fall in
cerebral oxygenation, and increased neural injury, suggesting that
alpha-adrenergic receptor activation after HI is an important endogenous
neuroprotective mechanism.