Abstract
We aimed to investigate the placental transfer of local anesthetics in perfusates with different pH values, using a dual-perfused human cotyledon model. The dual-perfused human cotyledon model was prepared from placentas obtained following cesarean delivery (n = 5). Protein-free solution was perfused through both maternal and fetal arteries. Four amide-type local anesthetics (mepivacaine [Mep]; lidocaine [Lid]; bupivacaine [Bup]; and ropivacaine [Rop]) were added to the maternal perfusate at 1 microg ml(-1). Three conditions were tested (stage 1, maternal pH 7.4, fetal pH 7.4; stage 2, maternal pH 7.4, fetal pH 6.9; and stage 3, maternal pH 6.9, fetal pH 6.9). Venous blood samples were collected from the fetal circuit after stabilization. The fetal vein/maternal artery concentration ratio (F/M ratio) of the local anesthetics was used as an index of placental transfer. The concentration of human chorionic gonadotropin (hCG) in the maternal vein was measured at the end of each stage. The F/M ratios in all stages were in the order of: Mep > Lid > Bup [symbol: see text] Rop. The F/M ratios of Mep were significantly higher than those of the other local anesthetics in all stages. The F/M ratios of Lid were higher than those of Rop in stages 2 and 3. The F/M ratios of Lid and Rop were higher in stage 2 than in stage 3. However, the differences between the F/M ratios in the three stages were not as large as expected from the basic uncharged ([B]) condition and pH gap. The concentration of hCG showed a time-dependent decrease with increasing stage (stage 1, 81.0 +/- 58.9 mIU ml(-1); stage 2, 57.4 +/- 31.8 mIU ml(-1); stage 3, 32.1 +/- 19.7 mIU ml(-1)). Our data clearly show that it is the basic uncharged concentration that mainly determines the placental transfer of amide-type local anesthetics with protein-free perfusate. This finding suggests that Rop and Bup can be used more safely than Mep in terms of placental transfer.
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