Evaluation of Sildenafil and Tadalafil for Reversing Constriction of Fetal Arteries in a Human Placenta Perfusion Model

Fetal growth restriction resulting from reduced placental blood perfusion is a major cause of neonatal morbidity and mortality. Aside from intense surveillance and early delivery, there is no treatment for fetal growth restriction. A potential treatment associated with placental vasoconstriction is the class of PDE5 (phosphodiesterase type 5) inhibitors such as sildenafil, which is known to cross the placenta. In contrast, tadalafil, a more potent and selective PDE5 inhibitor has not been studied in pregnancy or experimental models of fetal growth restriction. Therefore, we compared the efficacy of these 2 PDE5 inhibitors for reversing vasoconstriction in an ex vivo human placental model and evaluating molecular and physiological responses. Sildenafil and tadalafil were infused into the intervillous space in a preconstricted human placental dual cotyledon, dual perfusion assay for the comparison of arteriole pressures and molecular indicators of drug inhibition. Results indicate a decrease arterial pressu...