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The Effects of Low-Dose Endotoxin on the Umbilicoplacental Circulation in Preterm Sheep

Y. Garnier, MD,PhD

S. Supcun, MD

A. Jense, MD

Department of Obsterics and Gynecology, University of Maastricht, Maastricht, The Netherlands; Department of Obsterics and Gynecology, University of Bochum, Bochum, Germany

R. Berger, MD

Department of Obsterics and Gynecology, University of Maastricht, Maastricht, The Netherlands; Department of Obsterics and Gynecology, University of Bochum, Bochum, Germany; Marienhaus Klinikum, St. Elisabeth Neuwied, Klinik für Gynäkologie und Geburtshilfe, Friedrich-Ebert-Strasse 59, 56564 Neuwied, Germany; r.berger{at}nrh.st-elisabeth.de

T. H. M. Hasaart, MD,PhD

Department of Obsterics and Gynecology, University of Maastricht, Maastricht, The Netherlands; Department of Obsterics and Gynecology, University of Bochum, Bochum, Germany

Objective: In 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 eithe rthe 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 pressume (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 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 blood flow resulting in fetal hypoxemia without acidemia. These effects may be of significance in the development of fetal brain damage associated with intrauterine infection.

Key Words: Fetus • LPS • endotoxin • umbilical circulation • placental blood flow

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 289-293 (2004)
DOI: 10.1016/j.jsgi.2003.12.006


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