The effects of low-dose endotoxin on the umbilicoplacental circulation in preterm sheep

OBJECTIVE: hi the present study we examined the effects of low-dose endotoxin (lipopolysaccharides, LPS) on continuously recorded umbilical blood flow. METHODS: Twenty fetal sheep were catheterized at a gestational age of 107 +/- 1 days. A flow probe was placed around either the common umbilical artery or one single umbilical artery. Three days later fetuses received either 100 or 500 nanograms of LPS (n = 14) or 2 mL saline (n = 6) intravenously. Six fetuses died within 12 hours after LPS. Fetal heart rate (FHR), mean arterial pressure (MAP), and umbilical blood flow (Q(umb)) were monitored for 3 days. RESULTS: FHR increased by 25 +/- 4% at 4-5 hours after LPS (P < .01) and was elevated for 15 hours after LPS. MAP increased by 18 +/- 5% 1 hour after LPS (P < .01) and returned to control value 4-5 hours after LPS. Q(umb) began to decrease 1 hour after LPS and was minimal (-30 +/- 7%, P < .001) at 4-5 hours after LPS. Q(umb) slowly returned to the control value at 12 hours after LPS. Placental vascular resistance increased by 73 +/- 37% (P < .01), whereas pH did not appreciably change. CONCLUSION: Intravenous application of endotoxin caused a substantial and long-lasting decrease in umbilical bloodflow resulting in fetal hypoxemia without acidemia. These effects may be of significance in the development of fetal brain damage associated with intrauterine infection. Copyright (C) 2004 by the Society for Gynecologic Investigation.