Allison B J, Brain K L, Niu Y, Kane A D, Herrera E A, Thakor A S, Botting K J, Cross C M, Itani N, Skeffington K L, Beck C, Giussani D A
Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
Laboratorio de Función y Reactividad Vascular, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
J Physiol. 2016 Mar 1;594(5):1247-64. doi: 10.1113/JP271091.
Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.
尽管胎儿心血管系统对急性缺氧的防御机制及其潜在生理学原理已被确立数十年，但胎儿心血管系统如何应对慢性缺氧相对而言研究较少。我们设计并制造了等压缺氧舱，能够在可控的显著（10%氧气）缺氧条件下，使怀孕绵羊在较长孕期内维持该状态，从而使胎儿平均动脉血氧分压（P(aO2)）水平（11.5±0.6 mmHg）与缺氧妊娠的人类胎儿中测得的水平相似。我们还创建了一个无线数据采集系统，能够在缺氧妊娠发展过程中，除了记录自由活动母羊的胎儿血压和心率外，还能记录胎儿血流信号。我们确定了胎儿心血管功能在体内的纵向变化，包括在妊娠晚期并行测量胎儿颈动脉和股动脉血流以及氧气和葡萄糖输送情况。相对于胎儿股循环，在慢性缺氧期间及之后不久，输送到胎儿颈动脉的氧气（从2.7±0.2增至3.8±0.8；P<0.05）和葡萄糖（从2.3±0.1增至3.3±0.6；P<0.05）的比例增加。相比之下，正常氧合胎儿的氧气和葡萄糖输送与基线相比保持不变。慢性缺氧期间胎儿血浆尿酸盐浓度显著升高，而在正常氧合期间则无变化（差值：4.8±1.6 vs. 0.5±1.4 μmol l(-1)，P<0.05）。这些数据支持了所测试的假设，并表明在慢性缺氧胎儿中，底物输送持续从外周循环重新分配至重要循环，同时伴随着黄嘌呤氧化酶衍生的活性氧物种增加。
