Influence of reduced oxyhemoglobin affinity on cerebrovascular response to hypoxic hypoxia

Increasing P₅₀ (PO₂ at 50% oxyhemoglobin saturation) reduces cerebral blood flow (CBF) during arterial normoxia. We tested the hypothesis that increasing P₅₀ also diminishes the CBF response to isocapnic hypoxic hypoxia and that it reduces the response in proportion to the reduced normoxic CBF. P₅₀ was increased in nine unanesthetized newborn lambs from 26.3 ± 1.7 (±SE) to 36.6 ± 2.0 Torr by isovolemic exchange transfusion with low-affinity, adult sheep blood. Microsphere-determined CBF was decreased 22% during arterial normoxia. The slope of the response curve to reduced arterial O₂ content (Ca(O₂)) was proportionately attenuated by 26% with no change in O₂ uptake. Consequently, O₂ transport (CBF x Ca(O₂)) was reduced by a constant amount at each Ca(O₂) level. The percentage decrease in CBF at the higher P₅₀ was thus independent of Ca(O₂), and the percentage increase in CBF as Ca(O₂) fell was independent of P₅₀: the effects of P₅₀ and Ca(O₂) were independent. Common to alterations in both P₅₀ and Ca(O₂) are alterations in capillary and tissue PO₂. In this study the variable closest to capillary PO₂ was sagittal sinus PO₂. We found that when venous PO₂ was altered by changing Ca(O₂), the change in CBF was equivalent to that following the same alteration in venous PO₂ after a change in P₅₀. The percentage increase in venous PO₂ after exchange transfusion was approximately one-half that of the increase in P₅₀. About one-half of the potential increase in cerebral venous PO₂ was therefore eliminated by a compensatory reduction in cerebral O₂ transport over a wide range of Ca(O₂).