Effects of intermittent umbilical cord occlusions on metabolism, cardiovascular responses and brain injury in the ovine fetus.

摘要

Intermittent umbilical cord compressions may arise as a result of nuchal cords, uterine contractions and/or oligohydramnios. Birth asphyxia accounts for only 10% of all cases of cerebral palsy, pointing to the importance of events in the antepartum period as contributors to brain injury.;Forty four fetal sheep underwent placement of vascular catheters and an umbilical cord occluder at 122d gestation (term ∼ 147d). Animals were assigned to two studies, each with two experimental groups. In the Immediate Putdown Study, 7dUCO animals received repeated UCO of 2-min (days 1-6) and 4-min duration (Day7) every hour for 4hr, Naive animals received repeated UCO of 4-min duration on Day7 only. The fetuses were sacrificed 2hr after the final UCO on Day7 in both groups. In the Delayed Putdown Study, animals received the same treatments but were sacrificed 48-72 hr after the final UCO. The Control group received no UCO. Necrotic and apoptotic cell injury and VEGF and FLK-1 immunoreactivity in the parasagittal gray matter, periventricular white matter and the CA1 region of the hippocampus were studied by immunohistochemistry.;In both 7dUCO and Naive groups, each 4-min UCO on Day7, lead to similar blood gas and glucose alterations. However, lactate accumulation was significantly lower in the 7dUCO compared to the Naive group. In the 7dUCO group the latency to peak mean arterial blood pressure was significantly greater on Day 6 compared to Day1, and greater thereafter on Day7 compared to the Naive group.;VEGF was present in astrocytes, predominantly expressed in the layers 1-2 of the parasagittal cortex and was elevated with repeated UCO. FLK-1 was expressed in both neurons and astrocytes, evenly expressed throughout the parasagittal cortex and was not altered with repeated UCO. VEGF and FLK-1 were minimally expressed in the periventricular white matter and the CA1 region, and there were no changes in expression with UCO in either region.;The objective of this thesis was to understand more fully the effects of antenatal hypoxic preconditioning on fetal metabolism, cardiovascular responses and brain injury.;Very low levels of necrotic and apoptotic cells were found across all brain regions examined in each group with no differences in necrosis or apoptosis in the brains of the 7d000 compared to Naive animals.;In conclusion, fetal asphyxia in the absence of progressive acidemia is well tolerated by the ovine fetus in late gestation.;Key words: umbilical cord occlusions, hypoxia/asphyxia, preconditioning, brain injury, ovine fetus.