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

Abstract

Summary:The effect of hypoxemia and cephalic hy potension, alone and in combination, on hemispherical CBF and metabolism was examined in seven chronically catheterized fetal sheep. Hypoxemia was induced by low ering the maternal inspired oxygen fraction and cephalic hypotension was generated by partial occlusion of the fetal brachiocephalic artery. CBF was measured with ra dionuclide-labeled microspheres. During control, the ar terial blood oxygen content (Cao2) was 3.2 ± 1.0 (SO) mM and CBF averaged 131 ± 21 (SO) ml min -I 100 g -I.The cephalic perfusion pressure (PP, mean cephalic arte rial -sagittal venous) was 40 ± 4 mm Hg and cerebral vascular resistance (CVR, PP/CBF) was 0.31 ± 0.06 mm Hg ml-I min 100 g. During induced hypoxemia, Cao2 was 1.4 ± 0.7 mM and CBF was elevated to 223 ± 60 ml min -I 100 g -I. PP was not different from control and CVR was lower at 0.19 ± 0.04 mm Hg ml-I min 100 g, reflecting cerebral vasodilation. With cephalic hypoten sion alone (PP = 21 ± 4 mm Hg; Ca�? = 3.4 ± 0.9 mM), CBF fell to 83 ± 23 ml min -I 100 g--I and there was no significant change in CVR (0.26 ± 0.05 mm Hg ml-I min It has long been appreciated that fetal cerebral vasodilation and the subsequent increase in blood flow is a very important protective response to hypoxemia (Jones et aI. , 1977(Jones et aI. , , 1978. However, when the fetus becomes severely hypoxemic, the arterial blood pressure may not be maintained and the brain must also endure hypotension (Wagner et aI., 1986). Concomitant hypoxemia and hypoten- Abbreviations used: Cao2, arterial blood oxygen content; Csvo2, sagittal venous blood oxygen content; CVR, cerebral vascular resistance; 00, oxygen delivery; PP, perfusion pres sure.99 100 g). During combined hypoxemia and hypotension (Cao2 = 1.5 ± 0.8 mM and PP = 18 ± 4 mm Hg), CBF was significantly greater than during hypotension alone (l00 ± 6 ml min-I 100 g). CVR was 0. 19 ± 0.05 mm Hg ml-I min 100 g, identical to that measured in normoten sive hypoxemia and significantly less than found during hypotension alone. Cerebral oxygen consumption was lower during combined hypoxemia and cephalic hypoten sion than during hypoxemia alone. Cerebral glucose up take was significantly higher than control in both the hypoxemic and combined hypoxemic-hypotensive condi tions. The glucose:oxygen quotient (6 x molar glucose uptake/molar oxygen consumption) was not different from unity during control or hypotension but was 2.31 ± 1.16 and 3.63 ± 1.99 during the hypoxemic and hypox emic-hypotensive conditions, respectively, suggesting an anaerobic glucose utilization. No significant lactate efflux could be measured in any of these conditions.

Cerebral Histologic and Electrocorticographic Changes after Asphyxia in Fetal Sheep

“…Combined hypoxemia and hypotension lead to a significantly greater fall in cerebral oxygen consumption than hypoxemia alone (22). In this study, the fetal arterial BP during asphyxia was the most powerful predictor of subsequent parasagittal neuronal loss.…”

Cerebral Metabolism during Cord Occlusion and Hypoxia in the Fetal Sheep: A Novel Method of Continuous Measurement Based on Heat Production

“…The present results apply only to the cortex, a fairly homogenous region with respect to blood flow (Bishai et al 2003), and do not apply globally to brainstem, hippocampus and white matter, where flow responses to hypoxia differ (Ashwal et al 1984). There is also the possibility of a small but measurable contribution to total metabolism from anaerobic processes, even with normal O 2 delivery, but the absence of lactate in sagittal sinus blood and a glucose/oxygen quotient equal to 1, as well as previous work by others, argue against this possibility (Tsoulos et al 1972; Hohimer et al 1991; Turbow et al 1995).…”

“…However, during profound hypoxia, such as induced by umbilical cord occlusion, blood pressure and CBF decrease and oxygen use falls to negligible levels (Field et al 1990; Hunter et al 2003 a ). With such severe stress any residual energy production of the brain must depend on anaerobic pathways, normally quite limited in the adult (Chih et al 2001), but possibly of more importance in the fetus in accord with its increased tolerance to anoxic stress (Hohimer et al 1991; Singer, 1999; Van Cappellen et al 1999).…”

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

“…With models of maternal hypoxemia (e.g., high altitude or a low inspired oxygen fraction), fetal oxygenation falls while BP rises transiently, but then returns to normal, and then falls below normal [67,68,96,[103][104][105][106]. Perinatal hypoxic-ischemic encepatholpathy models that involve the entire body frequently use umbilical cord occlusion and are accompanied by reduced systemic fetal arterial oxygen tension and content [70,107,108].…”

“…The carotid arteries in the 0.65 sheep fetus are small and there is a relatively greater risk that commercially available occluders can inadvertently obstruct flow chronically if placement and routing techniques are not optimal. By contrast, the BCA is a larger and much more stable vessel for the placement of a single occluder [84,103]. In sheep, the BCA supplies the entire head, including the carotids, as well as both axillary arteries, which supply the forelegs.…”