Uncoupled Cerebral Blood Flow and Metabolism after Severe Global Ischemia in Rats

In a rat model of complete global brain ischemia (neck tourniquet) lasting either 3 min or 20 min, we monitored global CBF (sagittal sinus H₂ clearance) and CMRO₂ for 6 h to test the hypothesis that delayed postischemic hyperemia and uncoupling of CBF and CMRO₂ occur depending on the severity of the insult. Early postischemic hyperemia occurred in both the 3-min and 20-min groups (p < 0.05 vs. baseline values) and resolved by 15 min. Hypoperfusion occurred in the 3-min group between 15 and 60 min postischemia (≈23% reduction), and in the 20-min group from 15 to 120 min postischemia (≈50% reduction) (p < 0.05), and then resolved. CMRO₂ was not significantly different from baseline at any time after ischemia in the 3-min group. After 20 min of ischemia, however, CMRO₂ was decreased (≈60%) throughout the postischemic period (p < 0.05). At 5 min after ischemia, CBF/CMRO₂ was increased in both groups but returned to baseline from 60 to 120 min postischemia. In the 3-min group, CBF/CMRO₂ remained at baseline throughout the rest of the experiment. However, in the 20-min group, CBF/CMRO₂ once again increased (≈100%), reaching a significant level at 180 min and remaining so for the rest of the 6-h period (p < 0.05). These data demonstrate biphasic uncoupling of CBF and CMRO₂ after severe (20 min) global ischemia in rats. This relatively early reemergence of CBF/CMRO₂ uncoupling after 180 min of reperfusion is similar to that observed after prolonged cardiac arrest and resuscitation in humans.