THE PROSTACYCLIN ANALOG CARBACYCLIE, INCREASES TRANSFER IN PLACENTAE FROM PATHOLOGICAL PREGNANCIES

Abstract

The vasodilator prostacyclin (PGI2) is involved in the maintenance of blood flow in the placental vascular bed. Inhibition of PGI2 synthesis reduces diffusional transfer and increases vascular pressure in the perfused human placental lobe. Reduced umbilical PGI2 synthesis is characteristic of pregnancies complicated by pre-eclampsia, IUGR or maternal smoking. We have, therefore, assessed the effect of a PGI2 analogue, carbacyclin, on antipyrine (AP) clearance in dual-perfused placental lobes from normal and pathological pregnancies. Carbacyclin (1 and 10μM), administered in the maternal afferent circulation, had no effect on AP clearance or fetal afferent perfusion pressure in normal placentae. However, in placentae from pathological pregnancies (4 pre-eclamptics, 6 smoking mothers), administration of carbacyclin (1 and 10μM) resulted in a significant increase (19%, p<0.01 and 35%, p<0.001 respectively) in AP clearance over baseline values. Increased AP clearance in placentae from smoking mothers was accompanied by a decrease in fetal afferent pressure (2-3 mm Hg). Finally, subsequent perfusion of carbacyclin-free perfusate resulted in a return of both AP clearance and fetal afferent perfusion pressure to baseline values. These results suggest that maternally-administered carbacyclin effects blood flow and nutrient transfer in the pathological human placenta and could be considered in the therapeutic approach to pathological pregnancies associated with fetal growth retardation.