Abstract
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 compensating mechanisms are activated. We questioned whether MH, leading to mild acidosis, induces changes in cerebral metabolism. Metabolites in cerebrospinal fluid (CSF) samples, as analyzed by proton magnetic resonance spectroscopy, 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. In group II, MH with an intended pH of 7.23–7.27 was reached [start of MH (SMH)], and maintained during 2 h [end of MH (EMH)]. During SH, choline levels in CSF, a possible indicator of cell membrane damage, were increased. Both during SH and at EMH, CSF levels of lactic acid, alanine, phenylalanine, tyrosine, lysine, branched chain amino acids, and hypoxanthine were increased compared with control values and with SMH, respectively. At EMH, the hypoxanthine CSF-to-blood ratio was increased as compared with SMH. These results indicate that prolonged MH leads to energy degradation in the fetal lamb brain and may not be as safe as assumed.
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Abbreviations
- BBB:
-
blood-brain barrier
- BCAA:
-
branched chain amino acids
- BEecf:
-
extracellular fluid base excess
- bpm:
-
beats per minute
- carotid BF:
-
carotid blood flow
- Cao2:
-
arterial oxygen content
- Cvo2:
-
venous oxygen content
- Cavo2:
-
arteriovenous difference in oxygen content
- EAA:
-
excitatory amino acids
- EMH:
-
end of mild hypoxia
- FBP:
-
fetal blood pressure
- FHR:
-
fetal heart rate
- FID:
-
free induction decay
- Fio2:
-
fraction of oxygen in inspiratory gas
- 1H-NMR:
-
proton nuclear magnetic resonance
- MH:
-
mild hypoxia
- N:
-
normoxia
- nd:
-
not detectable
- Pco2:
-
carbon dioxide tension
- ppm:
-
parts per million
- SH:
-
severe hypoxia
- Sao2:
-
arterial oxygen saturation
- Svo2:
-
venous oxygen saturation
- SMH:
-
start of mild hypoxia
- 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 thank J. Joordens for invaluable help and assistance. Furthermore, we gratefully acknowledge the help of Dr. R.A. de Abreu, K. Wethly and A. Stegeman of the Laboratory for Pediatrics and Neurology for the measurement of the blood samples for purines and pyrimidines. We thank Henk van Lier for performing the statistical analyses with the linear mixed model.
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Van Cappellen Van Walsum, AM., Jongsma, H., Wevers, R. et al. Hypoxia in Fetal Lambs: A Study with 1H-NMR Spectroscopy of Cerebrospinal Fluid. Pediatr Res 49, 698–704 (2001). https://doi.org/10.1203/00006450-200105000-00015
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DOI: https://doi.org/10.1203/00006450-200105000-00015
