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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 3

Left and right ventricular cardiac dynamics in response to oxygen delivery.

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Left and right ventricular cardiac dynamics in response to oxygen delive...
Preterm fetal lambs that 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 demonstrated differential cardiac output responses to oxygen delivery. The relationship between ventricular cardiac output and oxygen delivery are shown for each ventricle. (A) In the left ventricle, hypoxemic fetuses demonstrated a reduced maximum cardiac output response (P < 0.0001) but a similar slope of the relationship between oxygen delivery and left ventricular cardiac output (P = 0.57) versus normoxic controls. (B) In contrast, in the right ventricle, both maximum cardiac output response (P < 0.0001) and the slope of the relationship between oxygen delivery and right ventricular cardiac output (P = 0.02) were reduced versus normoxic controls. Linear regression was performed to compare intercepts and slopes of the best-fit lines for the relationship between fetal oxygen delivery and cardiac output.

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