MECHANISMS OF MATERNOFETAL CHLORIDE TRANSFER ACROSS THE HUMAN PLACENTA PERFUSED IN-VITRO

To determine the relative contribution of the paracellular and transce llular routes to Cl- transfer, unidirectional maternofetal clearance ( K-mf) of Cl-36 was compared with K-mf of Cr-51-EDTA and creatinine acr oss the human placenta perfused in vitro. The effect of Cl- transport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and diphenylamine-2-carboxylate (DPC) was also investigated. The diffusio n coefficient (D) was estimated for each solute by use of an agar diff usion method. At steady state, K-mf/D for Cl-36 (0.070 +/- 0.003 cm, n = 23) was not different from that for Cr-51-EDTA (0.070 +/- 0.003 cm, n = 23), and K-mf/D was significantly higher for creatinine than for Cl-36 and Cr-51-EDTA (0.087 +/- 0.003 cm, n = 20, P < 0.001). Addition of the inhibitors DIDS and DPC to the perfusates resulted in a small but significant rise in K-mf of Cr-51-EDTA (0.41 +/- 0.03 vs. 0.49 +/- 0.02 ml/min, n = 16, P < 0.0001) and creatinine (0.66 +/- 0.05 vs. 0. 74 +/- 0.04 ml/min, n = 13, P < 0.001), but K-mf of Cl-36 was unchange d (1.11 +/- 0.07 vs. 1.13 +/- 0.05 ml/min, n = 16). There was no chang e in K-mf of any solute with time in control experiments. From these d ata, DIDS- and DPC-inhibitable fractions of K-mf for Cl-36 were estima ted and together accounted for 16% of total clearance. This study sugg ests that maternofetal flux of Cl-36 across the in vitro perfused huma n placenta occurs predominantly, but not solely, via paracellular rout es.