Abstract
Background
Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury.
Methods
Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was <8 mmHg. Neuronal injury was assessed after 72 h recovery.
Results
Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1–3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death.
Conclusion
Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment.
Impact
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It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep.
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Arginine vasopressin levels were elevated at 1–3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia.
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Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.
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Acknowledgements
The present study was funded by grants from the Health Research Council of New Zealand (grant number 17/601), the Auckland Medical Research Foundation (grant number 1108004) and New Zealand Lottery Grants Board (grant numbers 209214 and 340855). The funding sources had no role in the design or undertaking of the study, the interpretation of results, writing of the article nor the decision to submit this article for publication.
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These experiments were conducted in the Fetal Physiology and Neuroscience Group laboratory at the University of Auckland. A.J.G., P.P.D. and C.A.L. conceived the hypotheses, experimental design and analysis protocols for the study. C.A.L., P.P.D., J.O.D., and A.J.G. were responsible for data collection. C.A.L., M.K. and P.P.D. performed the analysis. C.A.L. drafted the manuscript. All authors were involved in data interpretation, in the editing and revision of the manuscript, approved the final version of the manuscript and agreed to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.
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Lear, C.A., Kasai, M., Drury, P.P. et al. Plasma vasopressin levels are closely associated with fetal hypotension and neuronal injury after hypoxia-ischemia in near-term fetal sheep. Pediatr Res 88, 857–864 (2020). https://doi.org/10.1038/s41390-020-0845-2
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DOI: https://doi.org/10.1038/s41390-020-0845-2
