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This study was undertaken to validate a new method of measuring cerebral metabolic rate in the fetal sheep based on heat production in a local region of the brain. Heat production was compared to oxygen use in 20 near-term fetuses during basal conditions, moderate hypoxia and cord occlusion. Thermocouples were placed to measure core and brain temperature(More)
Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at(More)
The blood anion nitrite contributes to hypoxic vasodilation through a heme-based, nitric oxide (NO)-generating reaction with deoxyhemoglobin and potentially other heme proteins. We hypothesized that this biochemical reaction could be harnessed for the treatment of neonatal pulmonary hypertension, an NO-deficient state characterized by pulmonary(More)
To investigate the role of nitric oxide (NO) in fetal cerebral circulatory responses to acute hypoxia, near-term fetal sheep were instrumented with laser Doppler probes placed in the parasagittal parietal cortices and vascular catheters in the sagittal sinus and brachiocephalic artery. After a 3 day recovery period, responses of cortical blood flow (CBF) to(More)
This study was undertaken to compare microsphere and laser Doppler flowmetry techniques for the measurement of cerebral blood flow, to assess the effect of probe implantation at the tip of the sensing probe and to measure brain tissue P(O2) (tP(O2)) in response to acute hypoxia. Fetal sheep of ~131 days gestation (n = 8) were chronically instrumented with(More)
Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the(More)
Accelerator MS (AMS) provides a novel method for obtaining and analyzing pharmacokinetics and pharmacodynamics in children. This paper reviews the scientific and ethical rationale for AMS in pediatric trials, the regulatory framework and general considerations with some specific examples of pediatric clinical trials using AMS. Microdosing in the context of(More)
This study was undertaken to measure the effects of mild hypothermia on cerebral blood flow and metabolism and cardiovascular responses to hypoxia in the fetal sheep. Near-term fetal sheep were chronically instrumented with laser Doppler flowmetry in the parietal cortex for measurement of relative changes in cerebral blood flow, as well as with arterial and(More)
A significant proportion of temporal lobe epilepsy (TLE), a common, intractable brain disorder, arises in children with febrile status epilepticus (FSE). Preventative therapy development is hampered by our inability to identify early the FSE individuals who will develop TLE. In a naturalistic rat model of FSE, we used high-magnetic-field MRI and long-term(More)
BACKGROUND Concern exists that extracorporeal membrane oxygenation (ECMO) may decrease cerebral blood flow (CBF), impair cerebral autoregulation, and thereby increase the risk of neurologic injury. OBJECTIVE This study was undertaken in newborn lambs to compare the effects of initiation of venoarterial and venovenous ECMO on CBF and cerebral oxygen(More)