Thresholds of focal cerebral ischemia in awake monkeys

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✓ 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 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites.

Middle cerebral artery 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 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours 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 about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed.

These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

Article Information

Address for Dr. DeGirolami: Department of Pathology (Neuropathology), University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605.

Address reprint requests to: Robert M. Crowell, M.D., Barrow Neurological Institute, 350 West Thomas Road, Phoenix, Arizona 85013.

© AANS, except where prohibited by US copyright law.

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Figures

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    Sites of cerebral blood flow recording. Drawing of horizontal whole brain section shows five electrode sites in the right (ischemic) hemisphere and one control electrode (R) on the left. Typical infarct is shown in stippled area.

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    Reversible ischemia. Neurological deficit is graded as follows: 1 = minimal, 2 = mild, 3 = moderate, 4 = severe. Each symbol on the chart represents flow from one electrode (see location on the horizontal section). Occlusion of the middle cerebral artery caused a moderate to severe deficit with profound ischemia at all electrode sites. After 17 minutes, reversal of occlusion led to complete recovery and a brief hyperemia. Pathological evaluation showed no infarction.

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    Irreversible infarction. Same symbols as in Fig. 2. Permanent middle cerebral artery occlusion caused a marked deficit and marked ischemia. Gradual mild improvement in deficit was noted over the 16-day survival period. Pathology showed a Grade 3 infarct encompassing the zones with lowest cerebral blood flow values.

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    Local cerebral blood flow (1CBF) and neurological deficit. Each point represents one monkey's average CBF determined from basal ganglia and capsule electrodes (usually 1 to 3). Note that decreasing average CBF correlates with increasing deficit. No deficit was detected if average CBF remained above about 23 cc/100 gm/min, an apparent paralysis threshold.

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    Local cerebral blood flow (1CBF) and infarction. Pooled data from animals undergoing middle cerebral artery (MCA) occlusion. Open circles represent electrodes in normal tissue. Triangles represent electrodes on the periphery of the infarct. Filled boxes represent electrodes located in infarcted tissue. Dashed line approximates an infarction threshold: when 1CBF falls below this critical value, infarction occurs.

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    Ischemia thresholds. When local cerebral blood flow (1CBF) falls below about 23 cc/100 gm/min, reversible paralysis occurs. Even profound ischemia is reversible for a brief time. When 1CBF falls below 10 cc/100 gm/min for 2 hours, or below 18 cc/100 gm/min during permanent occlusion, irreversible infarction occurs. MCA = middle cerebral artery.

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