Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland; Faculty of Health Sciences, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Obstetrics and Gynecology, St. George's Hospital, London, United Kingdom; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Am J Obstet Gynecol. 2021 Nov;225(5):544.e1-544.e9. doi: 10.1016/j.ajog.2021.04.228. Epub 2021 Apr 19.
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.
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.
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.
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=.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.
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.
硝苯地平是一种广泛应用于妊娠合并母体高血压疾病的药物，可能与胎盘功能不全和胎儿缺氧有关。关于缺氧时胎儿心肌对硝苯地平反应的证据有限。
我们假设硝苯地平在低氧环境下不会损害胎儿羊的心脏功能。特别是，我们研究了硝苯地平对胎儿心室功能参数和心输出量的影响。
本研究共纳入 21 只 122-134 天（足月 145 天）的慢性仪器化胎儿羊。通过二维斑点追踪和组织及频谱脉冲波多普勒超声心动图测量整体纵向应变、描述心室收缩和舒张功能的指数以及心输出量，评估胎儿心脏功能。通过有创监测胎儿颈动脉血压和血气值。在基线数据采集后，通过母亲高氧血症诱导胎儿低氧血症。在低氧血症期数据采集后，9 只胎儿接受硝苯地平输注，12 只胎儿接受生理盐水输注。在开始输注后 30 和 120 分钟收集数据。在 120 分钟数据采集后，母亲和胎儿的氧合正常化，同时继续输注，收集正常氧血症期数据。
低氧血症使胎儿颈动脉平均动脉压从 40（8）mmHg 降至 35（8）mmHg（P<.007），左心室整体纵向应变的变形小于基线（P=.001）。在低氧血症下，硝苯地平引起右心室整体纵向应变降低（P<.05），右心室等容舒张速度及其减速下降（P<.01），提示舒张功能障碍，右心室心输出量下降（P<.05）。硝苯地平并未改变胎儿左心室功能参数或心输出量。当恢复正常氧合时，胎儿右心室功能参数和心输出量恢复到基线水平。
在低氧胎儿中，硝苯地平损害右心室功能并降低其心输出量。当恢复正常氧合时，硝苯地平对胎儿右心室功能的不良影响被消除。我们的发现表明，在低氧环境中，硝苯地平对胎儿右心室功能产生有害影响。
