Urinary and cardiovascular responses to indomethacin infusion in the ovine fetus

Abstract

Our objective was to explore the urinary and cardiovascular responses of the near-term ovine fetus to plasma indomethacin levels similar to those in the human neonate undergoing indomethacin therapy. Chronically catheterized ovine fetuses between 125 and 139 days of gestation were studied. After a 1-hour control period we gave a bolus of 0.35 mg/kg estimated fetal weight of indomethacin into a fetal vein, followed by a 0.017 mg/kg/min continuous infusion for 5 hours (n = 9). Results were compared with a vehicle-infusion-only group (n = 10). During the first 3 hours of indomethacin infusion, fetal urinary output was increased by an average of 84.9% +/- 55.6% (analysis of variance, p less than 0.01). Urinary osmolality and sodium and chloride concentrations underwent sustained increases throughout the infusion period (p less than 0.001). Sodium excretion increased by 212% +/- 111% (p less than 0.05). Fetal arterial and venous pressures increased (p less than 0.001), and the change in urinary flow correlated positively with the change in arterial pressure (R = 0.55, p = 0.014). Fetal heart rate increased by 10% +/- 4% 1 hour after the bolus and remained elevated throughout the remainder of the infusion relative to vehicle-infused animals (p less than 0.001). Vehicle infusion had no effect on any fetal variable. This study does not support the hypothesis that indomethacin acutely reduces urinary flow rate in the late-gestation ovine fetus. Further, the observed urinary flow increases may be mediated in part by a pressure diuresis.