Prolonged reductions in placental blood flow and cerebral oxygen delivery in preterm fetal sheep exposed to endotoxin: possible factors in white matter injury after acute infection.
OBJECTIVE
Endotoxin causes hypoxemia and white matter injury in the preterm ovine fetus. Because cerebral hypoxia could contribute to brain injury, our objective was to determine the effects of endotoxin on regional cerebral oxygen (O(2)) delivery. To investigate causes of fetal hypoxemia, we also measured placental blood flow.


METHODS
We administered endotoxin (lipopolysaccharide, LPS) at 1 microgram/kg (intravenously) to 11 catheterized fetal sheep at approximately 0.7 of term; controls (n = 7) received saline. We measured fetal cerebral blood flow (CBF) and placental blood flow using microspheres, arterial blood gases, arterial pressure, and heart rate.


RESULTS
Seven fetuses survived LPS administration (LPS-S) and four died. LPS-S fetuses were hypoxemic at 4-8 hours after LPS. Fetal hemoglobin concentration and hematocrit increased by about 14% at 4 hours after LPS exposure, and mean arterial pressure decreased significantly from 4-8 hours. After LPS, CBF did not change significantly, but total cerebral O(2) delivery decreased by 35.7% at 4 hours and by 28.3% at 8 hours. O(2) delivery to cerebral white matter decreased below pre-LPS values at 4 hours (-35.9%) and 8 hours (-28.6%) after LPS. Relative to pre-LPS values, placental blood flow decreased by 53.3% at 4 hours and 43.0% at 8 hours after LPS.


CONCLUSIONS
Immature fetal sheep exposed to LPS had profound reductions in placental blood flow and cerebral O(2) delivery, which could contribute to fetal brain injury. Reduced O(2) delivery to white matter was similar to that in other brain regions. Mechanisms that enable fetal CBF to increase in hypoxemic conditions were apparently ineffective in the presence of LPS.
Dalitz
P
P
Fetal and Neonatal Research Group, Department of Physiology, Monash University, Victoria, Melbourne, Australia.
Harding
R
R
Rees
S M
SM
Cock
M L
ML
D000818:Animals; D001158:Arteries; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D020567:Fetal Weight; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008863:Microspheres; D009929:Organ Size; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D012756:Sheep; D014655:Vascular Resistance
D006454:Hemoglobins; D008070:Lipopolysaccharides; D002245:Carbon Dioxide; D010100:Oxygen