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Endotoxemia Severely Affects Circulation During Normoxia and Asphyxia in Immature Fetal Sheep

A. Coumans, MD

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

R. Berger, MD

Department of Obstetrics and Gynecology, University of Bochum, Bochum, Germany; Department of Obstetrics and Gynecology, University of Maastricht, Maastricht, The Netherlands; Universitätsfrauenklinik Bochum, Knappschaftskrankenhaus, In der Schornau 23 - 25, D-44892 Bochum, Germany. richard.berger{at}ruhr-uni-bochum.de

A. Jensen, MD

T. H. M. Hasaart, MD, PhD

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

Objective: The purpose of the present study was to determine whether endotoxins (lipopolysaccharides, LPS) affect the fetal cardiovascular system in a way likely to cause brain damage.

Methods: Thirteen fetal sheep were chronically instrumented at a mean gestational age of 107 ± 1 days. After control measurements of organ blood flow (microsphere method), blood gases, and acid base balance were obtained, seven of 13 fetuses received LPS (53 ± 3 µg/kg fetal weight) intravenously. Sixty minutes later, asphyxia was induced by occlusion of the maternal aorta for 2 minutes. Measurements of organ blood flows were made at -60, -1, +2, +4, +30, and +60 minutes.

Results: Unlike in the control group, after LPS infusion there was a significant decrease in arterial oxygen saturation (-46%; P <.001) and pH (P <.001). In LPS-treated fetuses the portion of combined ventricular output directed to the placenta decreased significantly (-76%; P <.001), whereas output to the fetal body (+60%; P <.001), heart (+167%; P <.05), and adrenals (+229%; P <.01) increased. Furthermore, during asphyxia circulatory centralization was impaired considerably in LPS-treated fetuses, and there was clear evidence of circulatory decentralization. This decentralization caused a severe decrease in cerebral oxygen delivery by 70%. Wihin 30 minutes after induction of asphyxia five of seven LPS-treated featuses died, whereas all control fetuses recovered completely.

Conclusions: Endotoxemia severely impaired fetal cardiovascular control during normoxia and asphyxia, resulting in a considerable decrease in cerebral oxygen delivery. These effects might have important effects in the development of fetal brain damage associated with intrauterine infection.

Key Words: Endotoxin • lipopolysaccharides • intrauterine infection • circulation • cerebral blood flow • cerebral ischemia • perinatal brain damage • fetal sheep • asphyxia

Journal of the Society for Gynecologic Investigation, Vol. 8, No. 3, 134-142 (2001)
DOI: 10.1177/107155760100800303


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