In fetal lambs, severe hypoxia (SH) will lead to brain damage. Mild hypoxia
(MH) is thought to be relatively safe for the fetal brain because compensa
ting mechanisms are activated. We questioned whether MH, leading to mild ac
idosis, induces changes in cerebral metabolism. Metabolites in cerebrospina
l fluid (CSF) samples, as analyzed by proton magnetic resonance spectroscop
y, were studied in two groups of seven anesthetized near-term fetal lambs.
In group I, SH leading to acidosis with an arterial pH <7.1 was achieved. I
n group II, MH with an intended pH of 7.23-7.27 was reached [start of MH (S
MH)], and maintained during 2 h [end of MH (EMH)]. During SH, choline level
s in CSF, a possible indicator of cell membrane damage, were increased. Bot
h during SH and at EMH, CSF levels of lactic acid, alanine. phenylalanine,
tyrosine, lysine, branched chain amino acids, and hypoxanthine were increas
ed compared with control values and with SMH. respectively. At EMH, the hyp
oxanthine CSF-to-blood ratio was increased as compared with SMH. These resu
lts indicate that prolonged MH leads to energy degradation in the fetal lam
b brain and may not be as safe as assumed.