Thresholds of focal cerebral ischemia in awake monkeys

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Abstract
An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain''s tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 min, 2-3 h or permanently. Serial monitoring evaluated neurological function, local CBF (H2 clearance) and other physiological parameters (blood pressure, blood gases and intracranial pressure). After 2 wk, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. MCA occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 h led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15-30 min of ischemia, moderate to large infarcts after 2-3 h of ischemia and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below .apprx. 23 cm3/100 g per min, reversible paralysis occurred. When local flow fell below 10-12 cm3/100 g per min for 2-3 h or below 17-18 cm3/100 g per min during permanent occlusion, irreversible local damage was observed. Some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization.