Effect of exogenous prostacyclin on central and uterine hemodynamics in the chronically instrumented pregnant guinea pig before and after indomethacin administration

Abstract

The effect of prostacyclin before and after pretreatment with indomethacin was studied in the chronically instrumented pregnant guinea pig. Twenty-six animals were studied between 45 and 65 days' gestation. Prostacyclin (6.25, 12.5, 25, 50, and 125 micrograms/kg/min) produced a dose-dependent decrease in arterial pressure (r = -0.915, p less than 0.0001) and uterine artery blood flow velocity, as measured by a miniaturized Doppler flow probe (r = -0.850, p = 0.0001), and an increase in heart rate (r = 0.745, p = 0.0335). Uterine resistance increased at each dose, with 125 micrograms/kg/min generating an increase greater than all others (p less than 0.02). The hypotensive effect of prostacyclin was blunted by indomethacin (p = 0.018). Rather than blunting the expected changes in the remaining parameters, pretreatment with indomethacin followed by prostacyclin significantly decreased uterine blood flow velocity further and increased uterine resistance. We conclude that prostacyclin infusion can have adverse effects on uterine blood flow and that these are altered by pretreatment with a prostaglandin synthetase inhibitor. Prostacyclin should be avoided in women with preeclampsia until further animal studies are available.