Cerebral Oxygenation during Postasphyxial Seizures in Near-Term Fetal Sheep

Abstract

After exposure to asphyxia, infants may develop both prolonged, clinically evident seizures and shorter, clinically silent seizures; however, their effect on cerebral tissue oxygenation is unclear. We therefore examined the hypothesis that the increase in oxygen delivery during postasphyxial seizures might be insufficient to meet the needs of increased metabolism, thus causing a fall in tissue oxygenation, in unanesthetized near-term fetal sheep in utero (gestational age 12571 days). Fetuses were administered an infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, followed by 10 mins of asphyxia induced by complete umbilical cord occlusion. The fetuses then recovered for 3 days. Sixty-one episodes of electrophysiologically defined seizures were identified in five fetuses. Tissue PO 2 (tPO 2 ) did not change significantly during short seizures (o3.5 mins), 5.270.2 versus baseline 5.670.1 mm Hg (NS), but fell to 2.270.2 mm Hg during seizures lasting more than 3.5 mins (Po0.001). During prolonged seizures, cortical blood flow did not begin to increase until tPO 2 had begun to fall, and then rose more slowly than the increase in metabolism, with a widening of the brain to blood temperature gradient. In conclusion, in the immature brain, during prolonged, but not short seizures, there is a transient mismatch between cerebral blood flow and metabolism leading to significant cerebral deoxygenation.

Regulation of cytochrome oxidase redox state during umbilical cord occlusion in preterm fetal sheep

“…Following a maternal midline abdominal incision and exteriorization of the uterus and either the top or bottom half of the fetus, catheters were placed in the left fetal femoral artery and vein, right axillary artery, and the amniotic sac. An ultrasonic blood flow probe (size 3S; Transonic Systems, Ithaca, NY) was placed around the left carotid artery to measure carotid blood flow as an index of global cerebral blood flow (19,23,52). Two small, flexible fiber optic probes for NIRS recordings were placed biparietally on the skull 3.0 cm apart, 1.5 cm anterior to bregma.…”

“…Multiplying this difference by carotid blood flow provides an index of relative heat production by the brain. As used presently, the validity of the method depends on left carotid artery flow accurately characterizing the flow through the brain tissue under study (19,20,23,27,52). It also requires that the temperature probe placed on the dura accurately reflects brain tissue temperature and that the core body temperature measured near the right atrium is a valid index of preductal arterial blood temperature.…”

Limited predictive value of early changes in EEG spectral power for neural injury after asphyxia in preterm fetal sheep

“…Electrocardiograph electrodes were sewn across the chest to record fetal heart rate. An ultrasonic blood flow probe (size 3S; Transonic Systems, Ithaca, NY) was placed around the left carotid artery to measure carotid blood flow as an index of global cerebral blood flow (25,37). Two pairs of EEG electrodes (AS633-7SSF, Cooner Wire, Chatsworth, CA) were placed on the dura bilaterally over the parasagittal parietal cortex (5 mm and 10 mm anterior to bregma and 5 mm lateral).…”

Asphyxia and Therapeutic Hypothermia Modulate Plasma Nitrite Concentrations and Carotid Vascular Resistance in Preterm Fetal Sheep

“…Further, in this paradigm, delayed seizures start approximately 6 to 12 hours after release of occlusion and resolve after * 36 to 72 hours. [32][33][34] Although in the preterm fetus, the individual events are typically relatively brief, 32 seizures can trigger increased metabolism with local vasodilation, 21 and so it is possible that they may also contribute to the secondary increase in nitrite levels.…”

“…A 3S ultrasound blood flow probe (Transonic Systems, Ithaca, New York) was placed around the left carotid artery to measure the carotid artery blood flow (CaBF) as an index of cephalic blood flow. [19][20][21] A thermistor (Incu-Temp-1, Mallinckrodt Medical Inc, St Louis) was placed over the parasagittal dura 20 mm anterior and 5 mm lateral to bregma and a second thermistor placed in the esophagus at the level of the right atrium. An inflatable silicone occluder (In Vivo Metric, Healdsburg, California) was placed around the umbilical cord of all fetuses.…”