Supplemental Digital Content is available in the text. The hypoxic fetus is at greater risk of cardiovascular demise during a challenge, but the reasons behind this are unknown. Clinically, progress has been hampered by the inability to study the human fetus non-invasively for long period of gestation. Using experimental animals, there has also been an inability to induce gestational hypoxia while recording fetal cardiovascular function as the hypoxic pregnancy is occurring. We use novel technology in sheep pregnancy that combines induction of controlled chronic hypoxia with simultaneous, wireless recording of blood pressure and blood flow signals from the fetus. Here, we investigated the cardiovascular defense of the hypoxic fetus to superimposed acute hypotension. Pregnant ewes carrying singleton fetuses surgically prepared with catheters and flow probes were randomly exposed to normoxia or chronic hypoxia from 121±1 days of gestation (term ≈145 days). After 10 days of exposure, fetuses were subjected to acute hypotension via fetal nitroprusside intravenous infusion. Underlying in vivo mechanisms were explored by (1) analyzing fetal cardiac and peripheral vasomotor baroreflex function; (2) measuring the fetal plasma catecholamines; and (3) establishing fetal femoral vasoconstrictor responses to the α1-adrenergic agonist phenylephrine. Relative to controls, chronically hypoxic fetal sheep had reversed cardiac and impaired vasomotor baroreflex function, despite similar noradrenaline and greater adrenaline increments in plasma during hypotension. Chronic hypoxia markedly diminished the fetal vasopressor responses to phenylephrine. Therefore, we show that the chronically hypoxic fetus displays markedly different cardiovascular responses to acute hypotension, providing in vivo evidence of mechanisms linking its greater susceptibility to superimposed stress.

中文翻译：

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慢性缺氧胎儿对低血压应激的心血管防御改变

补充数字内容在文本中可用。缺氧胎儿在挑战期间心血管死亡的风险更大，但其背后的原因尚不清楚。在临床上，由于无法以非侵入性方式研究长期妊娠的人类胎儿，进展受到阻碍。使用实验动物，当缺氧妊娠发生时，也无法在记录胎儿心血管功能的同时诱导妊娠缺氧。我们在绵羊妊娠中使用新技术，该技术将受控慢性缺氧的诱导与胎儿血压和血流信号的同步无线记录相结合。在这里，我们研究了缺氧胎儿对叠加急性低血压的心血管防御。从妊娠 121±1 天（约 145 天）开始，将携带通过导管和流量探头手术制备的单胎的怀孕母羊随机暴露于常氧或慢性缺氧环境中。暴露 10 天后，胎儿通过胎儿硝普钠静脉输注发生急性低血压。通过（1）分析胎儿心脏和外周血管舒缩压力反射功能来探索潜在的体内机制；(2)测定胎儿血浆儿茶酚胺；(3) 建立胎儿股骨血管收缩剂对 α1-肾上腺素能激动剂苯肾上腺素的反应。相对于对照组，长期缺氧的胎羊逆转了心脏和受损的血管舒缩压力反射功能，尽管在低血压期间血浆中的去甲肾上腺素和肾上腺素增加幅度相似。慢性缺氧显着降低了胎儿对去氧肾上腺素的血管加压反应。因此，我们表明长期缺氧的胎儿对急性低血压表现出明显不同的心血管反应，提供了将其更大的易感性与叠加压力联系起来的机制的体内证据。