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Fetal hypoxemia causes abnormal myocardial development in a preterm ex utero fetal ovine model
Kendall M. Lawrence, … , J. William Gaynor, Carlo R. Bartoli
Kendall M. Lawrence, … , J. William Gaynor, Carlo R. Bartoli
Published December 20, 2018
Citation Information: JCI Insight. 2018;3(24):e124338. https://doi.org/10.1172/jci.insight.124338.
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Resource and Technical Advance Reproductive biology Therapeutics

Fetal hypoxemia causes abnormal myocardial development in a preterm ex utero fetal ovine model

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Abstract

In utero hypoxia is a major cause of neonatal morbidity and mortality and predisposes to adult cardiovascular disease. No therapies exist to correct fetal hypoxia. In a new ex utero fetal support system, we tested the hypothesis that hypoxemic support of the fetus impairs myocardial development, whereas normoxic support allows normal myocardial development. Preterm fetal lambs were connected via umbilical vessels to a low-resistance oxygenator and placed in a sterile-fluid environment. Control normoxic fetuses received normal fetal oxygenation, and hypoxemic fetuses received subphysiologic oxygenation. Fetuses with normal in utero development served as normal controls. Hypoxemic fetuses exhibited decreased maximum cardiac output in both ventricles, diastolic function, myocyte and myocyte nuclear size, and increased myocardial capillary density versus control normoxic fetuses. There were no differences between control normoxic fetuses in the fetal support system and normal in utero controls. Chronic fetal hypoxemia resulted in significant abnormalities in myocyte architecture and myocardial capillary density as well as systolic and diastolic cardiac function, whereas control fetuses showed no differences. This ex utero fetal support system has potential to become a significant research tool and novel therapy to correct fetal hypoxia.

Authors

Kendall M. Lawrence, Samson Hennessy-Strahs, Patrick E. McGovern, Ali Y. Mejaddam, Avery C. Rossidis, Heron D. Baumgarten, Esha Bansal, Maryann Villeda, Jiancheng Han, Zhongshan Gou, Sheng Zhao, Jack Rychik, William H. Peranteau, Marcus G. Davey, Alan W. Flake, J. William Gaynor, Carlo R. Bartoli

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Figure 5

Myocardial histology.

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Myocardial histology.
Preterm fetal lambs received either normal oxygen ...
Preterm fetal lambs received either normal oxygen delivery (n = 9, 23 ± 1 ml/kg/min, 24 ± 2 days) or subphysiologic oxygen delivery (n = 7, 15 ± 1 ml/kg/min, 18 ± 2 days) in an ex utero fetal support system. At necropsy, myocardial histology was performed and compared to a group of control fetuses raised normally in utero (n = 8). (A) Myocardial capillary density was significantly reduced in control in utero fetuses (B) and control normoxic fetuses (C) compared with hypoxemic fetuses (D). There was no difference in myocardial capillary density between the control in utero fetuses and control normoxic fetuses (P = 0.48). Original magnification, ×20. Scale bars: 200 μm. (E–H) No difference in myocardial apoptosis was observed across experimental groups. A single TUNEL+ nucleus is shown (F inset). Original magnification, ×40. Scale bars: 40 μm. Statistical comparisons were made across groups with 1-way analysis of variance with Tukey’s post hoc tests to compare means between individual groups.

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