Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation

Abstract

BACKGROUND: Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited. OBJECTIVE: We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output. STUDY DESIGN: A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued. RESULTS: Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P<.007), and left ventricular global longitudinal strain showed less deformation than at baseline (P¼.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<.05). Nifedipine did not alter fetal left ventricular functional parameters or cardiac output. When normoxemia was restored, fetal right ventricular functional parameters and cardiac output returned to baseline level. CONCLUSION: In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.

Fetal myocardial deformation measured with two‐dimensional speckle‐tracking echocardiography: longitudinal prospective cohort study of 124 healthy fetuses

“…In this study, RV-GLS values were shown to be significantly higher throughout pregnancy compared with LV-GLS values. This finding is consistent with the results of other studies comparing LV-GLS and RV-GLS with advancing gestation 34,64,66 and in neonates 67 . Differences in ventricular myocardial architecture can explain the difference in GLS values between the two ventricles 68,69 .…”

“…The majority of its output is via the arterial duct and the descending aorta, as the pulmonary resistance is high due to the uninflated fluid-filled lungs limiting pulmonary blood flow 1 . In late gestation, with increased ductal sensitivity to changes in oxygen, saturation increases and this, along with placental maturation and increasing fetal blood pressure, affects the right ventricular afterload 1,63,64 . Changes in preload and afterload of both ventricles will be reflected in increased GLS and GLSR values.…”

A Sustainable Translational Sheep Model for Planned Cesarean Delivery of Contraction-Free Ewes

“…In contrast, sheep models used to answer research questions for humans often did not focus on animal survival. Even in studies with a neonatal focus, lambs and/or ewes have often been sacrificed [ 3 , 15 , 16 , 34 ]. As a result, there is little detailed information on how to follow up sheep after a planned CD, which represents a hurdle for obstetric researchers in developing new sheep models while maintaining animal welfare.…”

“…As CD is an operation that both the ewe and the lambs can survive, contemporary ethical and animal welfare considerations—such as the 3R principle—demand an appropriate study design that promotes maternal as well as neonatal well-being [ 14 ]. However, information on these topics is scarce, as it is still a common practice to euthanize both ewes and lambs after experiments [ 15 , 16 ]. Existing veterinary publications deal with the technique of performing CD under field conditions [ 17 – 21 ] and focus on emergency CD of ewes under labor due to complications such as failure of the cervix to dilate, fetal-maternal disproportion, or fetal malpresentation [ 20 , 22 ].…”

Effect of Nifedipine on Uterine and Middle Cerebral Artery Doppler in Pre-Eclampsia Patients

“…Recent study [16] in 2021, pointed the detrimental effect of Nifedipine on hypoxic fetus. From a clinical perspective, Nifedipine is a widely used medication in hypertensive patients where restricted fetal growth is not uncommon.…”