ABSTRACT
I. Introduction ................................................•..•............................................................... I
II. Description of the Method ............................................................................................ 2 A. Tissue Preparation ................................................................................................... 2 B. Perfusion Circuits ................................................................................................... 4 C. Perfusion Media ...................................................................................................... 5 D. Monitoring of the Two Perfusion Circuits ............................................................. 5
III. Validation of the Perfusion Method-Tissue Viability ............................................. 7 A. Pre-Perfusion Ischemia ........................................................................................... 7 B. Oxygen Consumption ............................................................................................. 9 C. Glucose Consumption ........................................................................................... l 0 D. Lactate Production ................................................................................................ II E. Protein Synthesis ................................................................................................... 12
IV. Placental Membrane Permeability for Hydrophilic Molecules .................................. 13
V. Reference Compounds for Placental Transfer Experiments ...................................... I5
VI. Application of the Dual/n Vitro Perfusion Technique to Toxicology and Pharmacology ....................................................................................................... I7 A. Membrane Permeability and Protein Binding ...................................................... I7 B. Metabolism of Drugs by Placental Tissue ........................................................... I9
VII. Summary ....................................................................... : ............................................. 20
Acknowledgments ................................................................................................................. 20
References ............................................................................................................................. 2I
C 199~ by CRC Preas. Inc. 1
Ethical as well as safety concerns for the mother and the infant impose substantial restrictions upon in vivo studies of the human placenta. Concentration measurements in maternal and cord blood at the time of delivery are of limited value, since one-point measurements do not reflect the dynamic state of concentration changes. Animal experiments are only a partially satisfactory alternative, since the placenta, like no other mammalian organ, presents an astonishing diversity in structure in different species which is expressed in differences in the cellular composition and the number of tissue layers separating maternal and fetal blood, as well as in the vascular arrangements, the relative direction, and the volume of blood flow in the two circulations.
