Non-steady state placental transfer of highly diffusible molecules

In twelve experiments performed on five pregnant sheep, uterine and umbilical venous blood samples were drawn in rapid succession following the beginning of a maternal arterial infusion of ethanol and antipyrine. Within a 20 s period the uterine venous ethanol/antipyrine concentration ratio increased from a minimum of 0.3 to 0.7 and the umbilical venous ethanol/antipyrine concentration ratio decreased from a maximum of 3 to 1.2. These results are in agreement with a model of placental exchange showing that the transfer rate of highly diffusible molecules is permeability limited at the beginning of the infusion and then rapidly becomes blood flow limited as the diffusing solutes accumulate in the placenta. The demonstration that the placental barrier is more permeable to ethanol than antipyrine, concomitant with previous demonstrations that the steady state placental clearances of ethanol and antipyrine are nearly equal, supports the hypothesis that in the steady state, the placental clearance of ethanol is blood flow limited.