Cerebral blood flow, oxygenation, and carbohydrate metabolism in immature fetal sheep in utero

Abstract

Studies of cerebral blood flow (CBF) and metabolism in fetal sheep have been largely confined to late gestation, a time when brain development in this species is largely complete. Few studies have been done at a time when the fetal sheep brain is in the midst of rapid differentiation and development. We studied seven fetal sheep in utero at 91 days of gestation (term = 145-150 days) 24 h after catheters were placed into the sagittal sinus, axillary artery, and inferior vena cava. We measured CBF by the microsphere method and used arteriovenous differences of O2, lactate, and glucose to calculate cerebral O2 consumption (CMRo2), fractional O2 extraction, glucose consumption, O2-glucose index (OGI), and cerebral lactate production. Compared with near-term fetal sheep, we found lower CBF (33.9 +/- 5.3 ml.100 g-1.min-1), lower glucose consumption (8.5 +/- 1.25 mumol.100 g-1.min-1), and lower CMRo2 (41.8 +/- 8.8 mumol.100 g-1.min-1). Fractional O2 extraction was 0.29 +/- 0.04, which is similar to near-term fetal sheep. There was consistent cerebral lactate production (2.45 +/- 1.58 mumol.100 g-1.min-1). The OGI was 81 +/- 16%, i.e., oxidative metabolism could account for 81% of glucose uptake. Lactate production accounts for virtually all glucose uptake exceeding that required for oxidation.

Spatial Heterogeneity in Oligodendrocyte Lineage Maturation and Not Cerebral Blood Flow Predicts Fetal Ovine Periventricular White Matter Injury

“…laboratories, and there is a high correlation of flows determined by radio-and fluorescent-labeled microspheres (Glenny et al, 1993;Bernard et al, 2000). Under basal conditions, our blood flow measurements in white and gray matter agreed closely with those obtained with radioactive microspheres (Szymonowicz et al, 1988(Szymonowicz et al, , 1990Gleason et al, 1989).…”

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

“…Another advantage of the fetal sheep model is that physiological studies can be performed at a critical stage of brain development, i.e., 90 days of gestation, in which there is brain growth and onset of organized electrocortical activity preceding a period of intense neuroglial multiplication and myelination (17). Finally, previous cerebrovascular studies in immature fetal sheep demonstrate that they have lower CBF and CMRO 2 as well as limited autoregulation and blunted responses to hypoxemia compared with near-term fetuses (9,10,13). A limitation of this model is the potential difficulty in extrapolating results obtained in fetuses to newborns, particularly the influence of the uteroplacental circulation and fetal physiology on the cerebrovascular and systemic responses we observed.…”

“…After the skin was prepared with povidone-iodine (Betadine), the uterus was exposed through a midline abdominal incision. The fetal head and limbs were exposed one at a time through small uterine incisions for placement of fetal catheters into the inferior vena cava (IVC, via pedal veins), the brachiocephalic trunk (via axillary arteries), the brachial/axillary vein, and the superior sagittal sinus by previously described methods (9,10). A catheter (Tygon tubing) was sewn to the fetal ear to measure amniotic fluid pressure and to administer ampicillin (500 mg).…”

The Effect of Combined Hypoxemia and Cephalic Hypotension on Fetal Cerebral Blood Flow and Metabolism

“…More recent measurements have shown that in normoxic fetal sheep, CBF and metabolism are modulated by its electroencephalographic ally de fined sleep-arousal state (Clapp, 1980;Richardson et aI., 1985b;Chao et aI., 1989b), with a small amount of anaerobic glucose metabolism appearing during the more metabolically active, low-voltage state. It also seems that more immature sheep fetuses studied be fore the development of distinguishable EEG arousal states consume glucose in excess of what can be ox idized and excrete lactate (Gleason et al, 1989).…”