Ovine intramembranous pathway permeability: use of solute clearance to determine membrane porosity

The contribution of the fetal chorioamniotic membranes (i.e. the intramembranous pathway) to the regulation and maintenance of amniotic fluid (AF) volume and composition has yet to be completely understood. Knowledge of membrane permeability properties is vital to understanding how the intramembranous pathway contributes to the overall maintenance of AF homeostasis. Although there are significant data regarding the regulation of intramembranous water flow, there is little understanding of the regulation of intramembranous solute flow. In the present study, we sought to determine the effect of molecular weight or size of non-polar compounds on intramembranous solute movement in the ovine model.

Five singleton ovine fetuses (117 +/- 3 days) were chronically prepared with bladder, tracheal, amniotic cavity and femoral arterial and venous catheters and an esophageal occluder. The allantoic membranes were excised. After 5 days' recovery, AF volume was calculated by intraamniotic injection of 99Tc-labelled red blood cells (time -6 to 0 h). At time 0, AF exchange routes were limited to the intramembranous pathway by inflation of the esophageal occluder and external drainage of fetal urine and lung fluid. Following intra-amniotic injection of creatinine (Cr, 1 g, MW 11 000 Da, 4 A) and [125I]albumin (RISA, 250 microCi, MW 69 000 Da, 36 A), maternal and fetal plasma and AF samples were collected at timed intervals during the subsequent 5 h. AF solute clearance (Cl(x)) was determined by the changes in AF total solute content.

Cr and RISA disappeared from the AF with a corresponding increase in fetal, though not maternal, plasma levels. The mean Cl(Cr) was significantly greater than Cl(RISA) (2.0 +/- 0.3 ml/min vs. 1.0 +/- 0.2 ml/min; p < 0.04).

Solute clearance from the amniotic cavity is inversely proportional to solute molecular weight/size. Although the membrane comprising the ovine intramembranous pathway is size restrictive, membrane pores allow passage of non-polar solutes up to 36 A. Knowledge of membrane permeability characteristics is essential for the utilization of the intramembranous pathway for fetal therapeutics.