Brain tolerance to middle cerebral artery occlusion during hypotension in primates

The aim of this study was to determine the duration of middle cerebral artery occlusion required to produce significant ischemic damage when the occlusion occurs during controlled systemic hypotension. In 21 anesthetized cynomolgus monkeys, an IV infusion of sodium nitroprusside was used to lower the mean arterial blood pressure to 45-50 mmHg for 90 minutes. Middle cerebral artery occlusion for 15, 30, 45, or 60 minutes was performed during the hypotensive period. Neurological function was then evaluated every 8 hours for a total of 72 hours. At the end of the observation period, the monkeys were again anesthetized, magnetic resonance imaging was performed, and the brain was perfused with 10% buffered formalin. Neurological deficits were observed after 30 minutes, but not after 15 minutes, of middle cerebral artery occlusion, and rapidly increased in incidence and severity when the duration of occlusion was increased. After 60 minutes of occlusion, all the monkeys exhibited severe deficits. Four monkeys died during the observation period--two in each of the 45- and 60-minute occlusion groups. Histopathological examination revealed that little or no ischemic damage resulted from a 15-minute occlusion during hypotension. However, severe ischemic damage began to occur after only 30 minutes of occlusion, and all monkeys subjected to middle cerebral artery occlusion for 60 minutes developed extensive regions of infarction. The size and incidence of these infarctions correlated well with the lesions observed in the magnetic resonance images. These results demonstrate that the duration of middle cerebral artery occlusion that produces cerebral infarction in primates is drastically reduced when the occlusion occurs at hypotensive levels commonly employed during neurovascular surgical procedures.