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 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. 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. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

中文翻译：

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近期胎羊低氧缺血后血浆加压素水平与胎儿低血压及神经元损伤密切相关

背景 需要敏感的生物标志物来快速识别缺氧缺血后的高危婴儿进行神经保护治疗。低血压是缺氧缺血性神经损伤的关键决定因素，也是包括血管紧张素-II 和精氨酸加压素在内的体液升压剂的强效刺激因素。因此，我们旨在量化由脐带闭塞 (UCO) 引起的缺氧缺血后潜伏期血管加压素和血管紧张素 II 水平与先前低血压和随后神经元损伤的严重程度之间的关系。方法 长期使用仪器的近期胎羊接受假 UCO 或 UCO 15 分钟或直到平均动脉压 <8 mmHg。恢复 72 小时后评估神经元损伤。结果 脐带闭塞与 UCO 后恢复的严重低血压有关；两个胎儿在 6 小时内出现严重继发性低血压并死亡。血管加压素水平而非血管紧张素 II 在 UCO 后 1-3 小时显着升高，并且与 UCO 期间低血压的严重程度以及随后矢状旁和外侧皮质、尾状核和壳核中神经元丢失的严重程度密切相关。血管加压素在 1 小时时的 Youden 临界点为 180.0 pmol/L，对严重神经元损伤或死亡的敏感性为 100%，特异性为 92.3%。结论 中重度缺氧缺血后不久的血管加压素水平可能是指导及时实施神经保护治疗的有用的早期生物标志物。影响 快速识别可能受益于治疗性低温的婴儿可能很困难。我们使用近期胎羊研究了缺氧缺血后早期血浆升压激素的增加是否是新生儿缺氧缺血性脑病的生物标志物。精氨酸加压素水平在缺氧缺血后 1-3 小时升高，可预测先前低血压的严重程度以及缺氧缺血后严重神经元损伤或死亡的风险。精氨酸加压素可能有助于在低体温治疗窗口的早期识别处于缺氧缺血性脑病高风险的新生儿。