Journal Article

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

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

2024

Overview

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 DO2 ${D_{{{\\mathrm{O}}_2}}}$and V̇O2 ${\\dot V_{{{\\mathrm{O}}_2}}}$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 DO2 ${D_{{{\\mathrm{O}}_2}}}$ . What is the central question of this study? Tadalafil is under consideration as an intervention strategy for fetal growth restriction: what is the impact of tadalafil on uterine artery blood flow, placental perfusion and fetal oxygen delivery? What is the main finding and its importance? Tadalafil does not increase uterine artery blood flow, placental perfusion or fetal oxygen delivery. Tadalafil may not be suitable as an intervention strategy for fetal growth restriction. The MRI techniques used herein would aid in the appropriate selection of future intervention strategies.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Blood / Blood flow / fetal development / fetal growth restriction / fetal MRI / Fetuses / Gestational age / haemodynamics / Heart / Magnetic resonance imaging / Perfusion / Placenta / placental perfusion / tadafer / tadalafil / Uterus / Vasodilation / Veins & arteries