Factors affecting human placental transfer of anesthesia-related drugs.

人双灌注子叶体外胎盘移植研究。我们采用双灌注人胎盘子叶（单通道模式）研究子宫和脐血流量及白蛋白浓度（蛋白结合）对异丙酚和局麻药胎盘转移的影响。对于异丙酚，胎盘转移增加(1)随着胎儿灌注液白蛋白浓度的增加，(2)随着母体血流量的增加，(3)随着胎儿血流量的增加。这种转移随着母体灌注液白蛋白浓度的增加而减少。异丙酚在胎盘组织中有明显的分散作用，而胎盘会起到凝血剂的作用。对于局麻药，胎儿(F)/母体(M)浓度比(1)随着不带电形式的增加而增加，即pH 7.4 （F和M）时pKa（甲哌卡因）降低，(2)胎儿灌注液pH降低。当两侧pH为6.9时，F/M比减小。罗哌卡因和布比卡因的F/M比值较小，具有较高的临床效价。综上所述，我们的模型使用清除率参数可以准确地表示药物的胎盘转移，而传统的母胎血浓度测定（F/M比）受子宫血流量、脐血流量和母脐血蛋白结合的影响极大。

Placental transfer of porpofol and local anesthetics in human dually perfused cotyledon in vitro.We investigated the effects of uterine and umbilical blood flow and albumin concentration (protein binding) on the placental transfer of propofol and local anesthetics by using the dually perfused human placental cotyledon (single pass mode). For propofol, placental transfer was incresed (1)with increasing albumin concentrations of the fetal perfusate, (2)with increasing maternal blood flow, and (3)with increasing fetal blood flow. The transfer was decreased with increasing albumin concentrations of maternal perfusate. Propofol significantly partitioned to placental tissues and the placenta would act as a condenser.For local anesthetics, fetal (F)/maternal (M) concentration ratio was increased (1)with increased uncharged form, namely lower pKa (mepivacaine) at pH 7.4 (F & M), (2)with lower pH in fetal perfusate. When pH in both sides became 6.9, F/M ratio was decreased. The F/M ratio was small in ropivacaine and bupivacaine which possess high clinical potency. In summary, our model could exactly denote the placental transfer of drug using the parameter of clearance while traditional determination of maternal and fetal blood concentration (F/M ratio) was extremely influenced with uterine blood flow, umbilical blood flow, and protein binding in maternal and umbilical blood).