Abstract
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 ≤ 7.00): glucose, lactate, pyruvate, hypoxanthine, alanine, β-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.
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Abbreviations
- BEecf:
-
extracellular fluid base excess
- carotid BF:
-
carotid blood flow
- Cao2:
-
arterial oxygen content
- Cvo2:
-
venous oxygen content
- Cavo2:
-
arteriovenous difference in oxygen content
- CSF:
-
cerebrospinal fluid
- FBP:
-
fetal blood pressure
- FHR:
-
fetal heart rate
- FID:
-
free induction decay
- 1H-NMR:
-
proton nuclear magnetic resonance
- IUP:
-
intrauterine pressure
- NO:
-
nitric oxide
- Sao2:
-
arterial oxygen saturation
- Svo2:
-
venous oxygen saturation
- TCA:
-
tricarboxylic acid
- TSP:
-
trimethylsilyl-2,2,3,3-tetradeuteropropionic acid
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Acknowledgements
The authors thank Theo Arts and Alex Hanssen of the Central Animal Laboratory Nijmegen, and Sjaak van Asten for their assistance. 1H-NMR spectra were recorded at the Dutch hf-NMR facility at the Department of Biophysical Chemistry, University of Nijmegen, The Netherlands (department head, Prof. C.W. Hilbers). We also thank J. Joordens for his invaluable help and assistance. Furthermore, we gratefully acknowledge the help of K. Wethly and A. Stegeman of the Laboratory for Pediatrics and Neurology for the measurement of the blood samples for purines.
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Van Cappellen Van Walsum, AM., Jongsma, H., Wevers, R. et al. 1H-NMR Spectroscopy of Cerebrospinal Fluid of Fetal Sheep during Hypoxia-Induced Acidemia and Recovery. Pediatr Res 52, 56–63 (2002). https://doi.org/10.1203/00006450-200207000-00012
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DOI: https://doi.org/10.1203/00006450-200207000-00012
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