Comparison of Cerebrovascular Response to Hypoxic and Carbon Monoxide Hypoxia in Newborn and Adult Sheep

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Abstract
Cerebral blood flow (CBF) responses to two types of isocapnic hypoxia, hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH), were examined in seven unanesthetized adult sheep by the radiolabeled microsphere technique. Comparisons were made with newborn lambs (5–12 days old) previously studied under similar conditions. The arterial O2 content (Cao2) was reduced in a graded manner to 50–60% of the control value. During HH, CBF increased to maintain cerebral O2 delivery (Cao2 x CBF) in both adults and newborns; however, cerebral O2 uptake (CMRO2) did not change. Although CMRO2 was higher in newborns, the responses of CBF/CMRO2 to HH did not differ significantly in newborns and adults. In newborns, regional CBF showed that brainstem areas were particularly responsive to HH. In both age groups, CBF increased to a greater extent with COH than with HH for similar reductions in Cao2. This resulted in an increase in cerebral O2 delivery with COH. The degree to which COH differed from HH correlated with the magnitude of the leftward shift of the oxyhemoglobin dissociation curve that accompanies COH. In adults, CMRO2 fell by 16% with COH but was maintained in newborns. We conclude that maintenance of cerebral O2 delivery during acute, isocapnic HH is a property of CBF regulation common to both newborn and adult sheep. During COH, the position of the oxyhemoglobin dissociation curve is an additional factor that sets the level of O2 delivery. The fetal conditions of low Cao2 and a left-shifted oxyhemoglobin dissociation curve may have provided the newborn with a microcirculation better suited for maintaining CMRO2 during COH.