BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal brain sparing in response to phenylephrine but not ephedrine

Joel Shapiro; Yehuda Ginosar; Yuval Gielchinsky; Uriel Elchalal; Zohar Bromberg; Nathalie Corchia-Nachmanson; Rinat Abramovitch

doi:10.1016/j.placenta.2019.11.006

BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal brain sparing in response to phenylephrine but not ephedrine

Placenta. 2020 Jan 15:90:52-57. doi: 10.1016/j.placenta.2019.11.006. Epub 2019 Nov 29.

Authors

Joel Shapiro¹, Yehuda Ginosar², Yuval Gielchinsky³, Uriel Elchalal³, Zohar Bromberg⁴, Nathalie Corchia-Nachmanson⁵, Rinat Abramovitch⁵

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
² Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel; Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA; Wohl Institute of Translational Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: ginosar@hadassah.org.il.
³ Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
⁴ The Goldyne Savad Institute of Gene Therapy and MRI Laboratory, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
⁵ Wohl Institute of Translational Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; The Goldyne Savad Institute of Gene Therapy and MRI Laboratory, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.

PMID: 32056552
DOI: 10.1016/j.placenta.2019.11.006

Abstract

Introduction: We previously reported blood oxygen level dependent MRI (BOLD-MRI) for monitoring placental and fetal hemodynamic changes in mice following maternal hypercapnia. Here we use BOLD-MRI to compare the placental and fetal hemodynamic effects of different maternal vasopressors in mice.

Methods: Pregnant ICR mice (n = 16; E17.5) anesthetized with pentobarbital (80 mg/kg i.p.) were placed supine in a 4.7-T Bruker Biospec MRI. Following baseline images, equipotential doses of ephedrine (10 mg/kg) or phenylephrine (10mcg/kg) were administered intravenously. Changes in placental and fetal signal were analyzed from T2*-weighted gradient echo MR images (TR/TE = 147/10 ms). Different regions of interest (placenta, fetal heart, fetal liver and fetal brain) were identified. Percentage change of BOLD-MRI signal intensity (SI) were presented as time curves.

Results: Ephedrine and phenylephrine elicited markedly different effects. Phenylephrine caused an approximate 50% reduction in placental, fetal heart and fetal liver BOLD-MRI-SI, but fetal brain BOLD-MRI-SI was unchanged (statistically different from placenta and other fetal organs; p < 0.001), and the fetal brain/liver BOLD-MRI-SI ratio was markedly increased versus baseline (p < 0.001). Following ephedrine, placental BOLD-MRI-SI increased 30% and fetal heart BOLD-MRI-SI was reduced 26%; other fetal organs were unchanged. Blood gases were unchanged.

Discussion: Phenylephrine induced BOLD-MRI-SI changes suggestive of placental and fetal hypoperfusion with brain sparing. Ephedrine induced BOLD-MRI-SI changes suggestive of increased cardiac output; we speculate that reduced fetal heart BOLD-MRI-SI may be due to increased fetal myocardial oxygen extraction or metabolic acidosis. The result demonstrates the potential of BOLD-MRI as a non-invasive hemodynamic tool for assessing pharmacodynamics effects in the placental and fetus.

Keywords: Animal models; Functional MRI; Pharmacodynamics; Placental blood flow; Vasopressors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / diagnostic imaging
Brain / drug effects*
Ephedrine / pharmacology*
Female
Fetus / diagnostic imaging
Fetus / drug effects*
Hemodynamics / drug effects
Magnetic Resonance Imaging
Mice
Phenylephrine / pharmacology*
Placenta / diagnostic imaging
Placenta / drug effects*
Pregnancy
Vasoconstrictor Agents / pharmacology*

Substances

Vasoconstrictor Agents
Phenylephrine
Ephedrine