1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery.
The purpose of the study was to investigate the sequence of processes occurring during and after hypoxia-induced acidemia. We used proton nuclear magnetic resonance spectroscopy, which provides an overview of metabolites in cerebrospinal fluid (CSF), reflecting neuronal metabolism and damage. The pathophysiological condition of acute fetal asphyxia was mimicked by reducing maternal uterine blood flow in 14 unanesthetized pregnant ewes. CSF metabolites were measured during hypoxia-induced acidemia, and during the following recovery period, including the periods at 24 and 48 h after the hypoxic insult. Maximum values of the following CSF metabolites were reached during severe hypoxia (pH <or= 7.00): glucose, lactate, pyruvate, hypoxanthine, alanine, beta-hydroxybutyrate, choline, creatine, myo-inositol, citrate, succinate, valine, and an unknown metabolite characterized by a resonance at 1.56 ppm in the proton nuclear magnetic resonance spectrum. Twenty-four hours after the hypoxic insult, myo-inositol was increased, and alanine was decreased 48 h after the hypoxic insult, both compared with control values. Choline levels in CSF had a linear relationship with arterial pH (r = 0.26, p < 0.005). During severe hypoxia, CSF levels of succinate and choline are increased. Increased CSF levels of succinate may indicate dysfunction of the mitochondrial respiratory chain, whereas elevated CSF choline levels may indicate disrupted cell membranes. The increase of the CSF myo-inositol level after 24 and 48 h may indicate osmolytic cell changes causing cell edema. Decreased alanine level may represent changes in the source of excitatory amino acid synthesis.
Van Cappellen Van Walsum
Anne-Marie
AM
Department of Obstetrics and Gynecology, University Medical Centre St. Radboud, Nijmegen, The Netherlands.
Jongsma
Henk W
HW
Wevers
Ron A
RA
Nijhuis
Jan G
JG
Crevels
Jane
J
Engelke
Udo F H
UF
De Abreu
Ronny A
RA
Moolenaar
Sytske H
SH
Oeseburg
Berend
B
Nijland
Roel
R
D020155:3-Hydroxybutyric Acid / Q000134:cerebrospinal fluid; D000138:Acidosis / Q000134:cerebrospinal fluid*; D000818:Animals; D002794:Choline / Q000134:cerebrospinal fluid; D019343:Citric Acid / Q000134:cerebrospinal fluid; D003404:Creatinine / Q000134:cerebrospinal fluid; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D019271:Hypoxanthine / Q000134:cerebrospinal fluid; D000860:Hypoxia / Q000134:cerebrospinal fluid*; D007294:Inositol / Q000134:cerebrospinal fluid; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D009682:Magnetic Resonance Spectroscopy; D011247:Pregnancy; D011522:Protons; D019289:Pyruvic Acid / Q000134:cerebrospinal fluid; D012756:Sheep; D019802:Succinic Acid / Q000134:cerebrospinal fluid; D014633:Valine / Q000134:cerebrospinal fluid
D011522:Protons; D019343:Citric Acid; D019271:Hypoxanthine; D019344:Lactic Acid; D007294:Inositol; D019289:Pyruvic Acid; D019802:Succinic Acid; D003404:Creatinine; D014633:Valine; D005947:Glucose; D002794:Choline; D020155:3-Hydroxybutyric Acid