ABSTRACT
Complete global cerebral ischemia refers to situations in which cerebral blood fl ow (CBF) falls to zero, such as in the case of cardiac arrest. Incomplete global cerebral ischemia refers to situations in which CBF does not completely cease but falls suffi ciently to impair cellular processes, metabolism, and function. Incomplete ischemia arises from various causes of arterial hypotension, shock, and intracranial hypertension. The brain requires a continuous supply of oxygen and glucose for normal function. With the sudden onset of complete cerebral ischemia, consciousness can be lost within 10 sec, and the electroencephalogram (EEG) can become isoelectric within 20 sec.The onset of isoelectric EEG is associated with ( i ) an effl ux of potassium ions (K + ) that increases the extracellular concentration from ∼3-12 mM, and ( ii ) a moderate increase in intracellular calcium ions (Ca 2+ ) ( 1,2 ). Because of the high rate of oxidative metabolism in the brain, phosphocreatine becomes largely depleted within 1 min, and adenosine triphosphate (ATP) becomes depleted within 2 min of the onset of complete ischemia ( 3,4 ). When ATP falls to ∼30% of normal levels, the cells depolarize, causing an additional large effl ux of K + , an increase in extracellular K + in excess of 60 mM, and a large infl ux of sodium (Na + ), Ca 2+ , and water. Consequently, the extracellular space shrinks and the cells swell. The continued consumption of ATP and anaerobic glycolysis of glycogen and glucose stores generate a large proton load in the cell. The intracellular pH gradually falls from 7.1 to ∼6.2 over the fi rst 6 min of cardiac arrest ( 5 ). The lack of clearance of CO 2 by blood fl ow contributes to the fall in pH. Therefore, complete lack of CBF initiates a rapid sequence of disturbances in cell homeostasis ( Fig. 1 ).
