Criteria of viability in isolated brain preparations

Isolated brains were perfused for 30 min at 10, 20, 30 or 40 torr followed by up to 45 min of reoxygenation. Arterial and venous blood samples were drawn at frequent intervals before, during and after hypoxia for determination of oxygen and glucose content. Brain samples were frozen in situ before hypoxia, following 30 min of hypoxia and after 45 min of reoxygenation for measurement of adenine nucleotide and creatine phosphate (CrP) content. Neither the cerebral metabolic rate for oxygen (CMRO2) nor the ATP level returned to normal in the arterial pO2 10 and 20 torr groups. Although ATP reached normal levels in the arterial pO2 30 torr group following 45 min of reoxygenation. CMRO2 was 84% of normal and the CrP was only 63% of normal. However, ATP, CMRO2 and CrP were all normal in the arterial pO2 40 torr group following 45 min of reoxygenation. The failure of the arterial pO2 30 torr group to reach a normal CrP level is thought to be the result of a defect in brain energy metabolism whereby the cell was unable to generate ATP at a rate sufficient to restore CrP to normal levels. The defect appears to be signaled by a lower than normal CMRO2. The ability to effectively utilize oxygen to form ATP is believed to reside in the intact mitochondria of undamaged brain cells. Thus, the posthypoxic CMRO2 is an index of mitochondrial function and by implication it is a measure of the integrity of cerebral neurons.