Leena Alanne1, Amarnath Bhide2, Juulia Lantto3, Heikki Huhta4, Merja Kokki5, Mervi Haapsamo3, Ganesh Acharya6, Juha Räsänen7. 1. Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland; University of Eastern Finland, Faculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, Kuopio, Finland. 2. Department of Obstetrics and Gynecology, St. George's Hospital, London, United Kingdom; Women's Health & Perinatology Research Group; Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway. 3. Department of Obstetrics and Gynecology, Oulu University Hospital and University of Oulu, Oulu, Finland. 4. Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland. 5. Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland. 6. Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. 7. Fetal Medicine Center, Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address: juha.rasanen@hus.fi.
Abstract
BACKGROUND: Nifedipine is 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. Especially, 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 122-134 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 2D 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 hypoxygenation. Following 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 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) mmHg to 35 (8) mmHg (p <0.007), 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. CONCLUSIONS: 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 hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.
BACKGROUND:Nifedipine is 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. Especially, 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 122-134 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 2D 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 hypoxygenation. Following 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 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) mmHg to 35 (8) mmHg (p <0.007), 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. CONCLUSIONS: In hypoxemic fetus, nifedipineimpaired 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 hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.
Authors: N H M van Oostrum; C M de Vet; S B Clur; D A A van der Woude; E R van den Heuvel; S G Oei; J O E H van Laar Journal: Ultrasound Obstet Gynecol Date: 2022-04-06 Impact factor: 8.678