Induction of controlled hypoxic pregnancy in large mammalian species
Induction of controlled hypoxic pregnancy in large mammalian species
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DOI：
10.14814/phy2.12614
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发表时间：
2015-12-01
影响因子：
2.5
通讯作者：
Giussani, Dino A.
中科院分区：
文献类型：
--
作者：
Brain, Kirsty L.;Allison, Beth J.;Giussani, Dino A.
大型哺乳动物妊娠合并慢性缺氧的研究进展一直受到阻碍，因为无法测量胎儿氧合的长期显著降低，其值与人类妊娠合并胎儿生长限制的测量值相似。在这里，我们介绍了一种生理研究技术，该技术能够使长期使用仪器的母羊和胎羊在超过可居住的高海拔水平的显著和可控的孤立慢性缺氧条件下延长妊娠期。这种慢性缺氧模型允许在挑战实际发生时测量母胎血气。使用该模型，这种程度和持续时间的慢性缺氧概括了人类高危妊娠后代中显著的不对称生长限制、明显的心肌病和内皮功能丧失，为治疗研究打开了一扇新的窗口。
Progress in the study of pregnancy complicated by chronic hypoxia in large mammals has been held back by the inability to measure long-term significant reductions in fetal oxygenation at values similar to those measured in human pregnancy complicated by fetal growth restriction. Here, we introduce a technique for physiological research able to maintain chronically instrumented maternal and fetal sheep for prolonged periods of gestation under significant and controlled isolated chronic hypoxia beyond levels that can be achieved by habitable high altitude. This model of chronic hypoxia permits measurement of materno-fetal blood gases as the challenge is actually occurring. Chronic hypoxia of this magnitude and duration using this model recapitulates the significant asymmetric growth restriction, the pronounced cardiomyopathy, and the loss of endothelial function measured in offspring of high-risk pregnancy in humans, opening a new window of therapeutic research.