Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe

Jack R.T. Darby*, Dimitra Flouri, Steven K.S. Cho, Georgia K. Williams, Stacey L. Holman, Ashley S. Meakin, Michael D. Wiese, Anna L. David, Christopher K. Macgowan, Mike Seed, Andrew Melbourne, Janna L. Morrison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116–117 days’ gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120–123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15–75 min (TAD 1) and ∼75–135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation—‘DECIDE’ technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal (Formula presented.) and (Formula presented.) were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal–placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA (Formula presented.).

Original languageEnglish
Pages (from-to)980-991
Number of pages12
JournalExperimental Physiology
Volume109
Issue number6
Early online date12 Apr 2024
DOIs
Publication statusPublished - 1 Jun 2024

Keywords

  • fetal development
  • fetal growth restriction
  • fetal MRI
  • haemodynamics
  • magnetic resonance imaging
  • placental perfusion
  • tadafer
  • tadalafil

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