Base-line O₂ extraction influences cerebral blood flow response to hematocrit

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O₂ content (Ca(O₂)). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O₂ demand (cerebral O₂ consumption, CMR(O₂) to supply (cerebral O₂ transport: OT = CBF x Ca(O₂)) and is assumed to be inversely related to tissue O₂ availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO₂ partial pressure (Pa(CO₂)) = 15.3 ± 0.7 mmHg, means ± SE; n = 7] or hypercarbia (Pa(CO₂) = 62.7 ± 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 ± 0.5%) with no significant increase in Ca(O₂). Pa(CO₂) was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change. CBF corrected for any individual alteration in CMR(O₂), i.e., CBF/CMR(O₂), decreased after methemoglobin exchange transfusion in both hypercarbic (38.9 ± 6.1 to 26.3 ± 4.2 ml/ml O₂) and hypocarbic (14.7 ± 1.3 to 13.1 ± 0.7 ml/mlO₂) animals; however, the mean percentage decrease was significantly greater in the low E hypercarbic animals than in the high E hypocarbic animals (32.0 ± 3.3 vs 9.2 ± 5.2%, P < 0.01). This study supports the hypothesis that the magnitude of the decline in CBF secondary to an increase in RBC concentration depends on the initial E. The effect of RBC concentration on CBF is greatest when E is low (i.e., when O₂ availability is high).