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Factors affecting human placental transfer of anesthesia-related drugs.

影响麻醉相关药物人胎盘转移的因素。

基本信息

批准号：
14370498
负责人：
TASHIRO Chikara
金额：
$ 9.02万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

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).

异丙酚和局麻药在体外人胎盘绒毛叶中的传递研究我们采用人胎盘绒毛叶（单程）双灌注模型，研究了子宫和脐带血流量以及白蛋白浓度（蛋白结合）对异丙酚和局麻药在胎盘绒毛叶中传递的影响。对于丙泊酚，胎盘转移增加（1）随着胎儿灌注液中白蛋白浓度的增加，（2）随着母体血流量的增加，（3）随着胎儿血流量的增加。随着母体灌流液中白蛋白浓度的增加，转移减少。异丙酚在胎盘组织中的分配作用明显，胎盘组织起浓缩器的作用，局部麻醉药中，胎儿（F）/母体（M）浓度比随着不带电形式的增加而增加，即在pH7.4时pKa值较低（F & M），（2）胎儿灌流液pH值较低。当两侧pH值均为6.9时，F/M比值降低。罗哌卡因和布比卡因的F/M比值较小，具有较高的临床效力。总之，我们的模型可以使用清除率参数准确地表示药物的胎盘转移，而传统的母体和胎儿血液浓度（F/M比）的测定受到子宫血流量、脐带血流量以及母体和脐带血中蛋白结合的极大影响。