Ducsay C A, Umezaki H, Kaushal K M, Barrish A, Gilbert J, Manson J
Department of Physiology, School of Medicine, Loma Linda University, CA 92350, USA.
Am J Obstet Gynecol. 1996 Jul;175(1):50-5. doi: 10.1016/s0002-9378(96)70250-8.
The purpose of this study was to determine the extent of placental transfer of the angiotensin-converting enzyme inhibitor enalaprilat and the effects on maternal and fetal cardiovascular parameters.
Between gestational days 122 and 126 (term 167 days) five rhesus macaques underwent surgery for implantation of maternal and fetal vascular catheters. At least 4 days after surgery maternal and fetal blood pressures and heart rates were recorded for 1 hour. This was followed by a 5-minute maternal venous infusion of saline solution vehicle and recording for an additional hour. Enalaprilat was then infused over 5 minutes through the maternal femoral artery at doses of 0.05, 0.1, or 0.2 mg/kg. Maternal and fetal arterial blood samples were collected for determination of blood gas status and plasma enalaprilat concentrations.
Enalaprilat rapidly crossed the placenta, and fetal values for areas under the concentration time curve were 50% to 65% of maternal values across dose groups. Drug was retained in the fetal plasma approximately threefold to fourfold longer than in maternal plasma. Maternal heart rate, blood pressure, arterial Po2 and pH were unchanged after enalaprilat infusion, as were fetal heart rate and blood gases. In contrast, fetal arterial pressure decreased significantly (19% to 23%, p < 0.01) after maternal treatment with 0.1 and 0.2 mg/kg and remained depressed throughout the 6-hour study interval. At 0.05 mg/kg fetal arterial pressure was decreased by 13% from baseline; differences were not significantly different (p > 0.05).
Results from this study indicate that enalaprilat rapidly crosses the primate placenta with a single intravenous administration to the mother, resulting in significant and prolonged reduction of fetal arterial pressure. Because maternal cardiovascular parameters were unaffected, enalaprilat appears to have a direct effect on fetal arterial pressure.
本研究旨在确定血管紧张素转换酶抑制剂依那普利拉的胎盘转运程度及其对母体和胎儿心血管参数的影响。
在妊娠第122至126天（足月为167天），对5只恒河猴进行手术，植入母体和胎儿血管导管。术后至少4天，记录母体和胎儿的血压及心率1小时。随后进行5分钟的母体静脉输注生理盐水载体，并再记录1小时。然后通过母体股动脉在5分钟内输注依那普利拉，剂量分别为0.05、0.1或0.2mg/kg。采集母体和胎儿动脉血样本，用于测定血气状态和血浆依那普利拉浓度。
依那普利拉迅速穿过胎盘，各剂量组胎儿浓度-时间曲线下面积值为母体值的50%至65%。药物在胎儿血浆中的保留时间比母体血浆长约三至四倍。输注依那普利拉后，母体心率、血压、动脉血氧分压和pH值均未改变，胎儿心率和血气也未改变。相比之下，母体用0.1和0.2mg/kg治疗后，胎儿动脉压显著降低（19%至23%，p<0.01），并在整个6小时研究期间持续降低。0.05mg/kg时，胎儿动脉压较基线降低13%；差异无统计学意义（p>0.05）。
本研究结果表明，单次静脉注射给母体依那普利拉后，其迅速穿过灵长类胎盘，导致胎儿动脉压显著且持续降低。由于母体心血管参数未受影响，依那普利拉似乎对胎儿动脉压有直接作用。
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