University of Oulu

Alanne L, Bhide A, Lantto J, et al. Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation. Am J Obstet Gynecol 2021;225:544.e1-9, ISSN 0002-9378,

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

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Author: Alanne, Leena1,2; Bhide, Amarnath3,4; Lantto, Juulia5;
Organizations: 1Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland
2Faculty of Health Sciences, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
3Department of Obstetrics and Gynecology, St. George’s Hospital, London, United Kingdom
4Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
5Department of Obstetrics and Gynecology, Oulu University Hospital and University of Oulu, Oulu, Finland
6Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
7Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland
8Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway
9Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
10Fetal Medicine Center, Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2022-01-26


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(P=0.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<0.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<0.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<0.05). 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.

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Series: American journal of obstetrics and gynecology
ISSN: 0002-9378
ISSN-E: 1097-6868
ISSN-L: 0002-9378
Volume: 225
Issue: 5
Pages: 544.e1 - 544.e9
DOI: 10.1016/j.ajog.2021.04.228
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
3111 Biomedicine
Funding: This research was funded, in part, by a grant from the Regional Health Authority of Northern Norway and, in part, by a salary from the University of Eastern Finland.
Copyright information: © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (