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Transient Umbilical Cord Occlusion in Late-Gestation Fetal Sheep Results in Hippocampal Damage but Not in Cerebral Arteriovenous Difference for Nitrite, a Stable End Product of Nitric Oxide

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Abstract

Objective

To investigate the effect of total umbilical cord occlusion on cerebral arteriovenous difference for nitrite (a stable end product of nitric oxide) and neuronal outcome.

Method

The cord was totally occluded for 10 minutes in 14 late-gestation (gestational age 113-120 days) chronically instrumented fetal sheep. Arterial (carotid artery) and venous (superior sagittal sinus) blood samples were taken at regular intervals for determination of acid-base status, glucose, lactate, and nitrite plasma levels. Three days after the occlusion period the fetal brain was perfusion fixed, and the parietal cortex, hippocampus, and cerebellum were scored for neuronal damage.

Results

Three fetuses died shortly after the occlusion period. Total umbilical cord occlusion resulted in a combined respiratory and metabolic acidosis as observed in carotid arterial blood gas samples (pH, 6.96 ± 0.02; CaO2 [mmol/L], 0.43 ± 0.9; Paco2 [kPa], 13.46 ± 0.38; base excess [mmol/L], -11.1 ± 0.8; lactate [mmol/L], 10.57 ± 0.95; bradycardia, 75 ± 9 bpm; and hypotension, 29.85 ± 3.00 mmHg) (n = 14, values are mean ± standard error of the mean). Selective brain damage was observed in the hippocampus in 10 of the 11 surviving fetal sheep. No changes in arterial, venous, or cerebral arteriovenous difference for nitrite plasma levels were observed (n = 11).

Conclusion

Total umbilical cord occlusion of 10 minutes in preterm fetal sheep results in hippocampal damage but not in changes of cerebral arteriovenous difference for nitrite plasma levels, a stable end product of nitric oxide.

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Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, and Surgery, University Hospital Maastricht, PO Box 5800, 6202 AZ, Maastricht, The Netherlands

    Han Keunen MD, Nicolaas E. P. Deutz MD, PhD, Jos L. H. Van Reempts & Tom H. M. Hasaart MD, PhD

  2. Department of Life Sciences, Janssen Research Foundation, Beerse, Belgium

    Han Keunen MD, Nicolaas E. P. Deutz MD, PhD, Jos L. H. Van Reempts & Tom H. M. Hasaart MD, PhD

Authors
  1. Han Keunen MD
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  2. Nicolaas E. P. Deutz MD, PhD
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  3. Jos L. H. Van Reempts
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  4. Tom H. M. Hasaart MD, PhD
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Corresponding author

Correspondence to Tom H. M. Hasaart MD, PhD.

Additional information

This work was supported by the University Maastricht Research Fund.

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Keunen, H., Deutz, N.E.P., Van Reempts, J.L.H. et al. Transient Umbilical Cord Occlusion in Late-Gestation Fetal Sheep Results in Hippocampal Damage but Not in Cerebral Arteriovenous Difference for Nitrite, a Stable End Product of Nitric Oxide. Reprod. Sci. 6, 120–126 (1999). https://doi.org/10.1177/107155769900600302

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