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SUMMARYWe developed a monkey model of 16 minutes global brain ischemia (GBI) resulting in reproducible, severe, permanent functional neurologic deficit with long term (7 days) postischemic (PI) survival made possible by standardized intensive care with 24 hour coverage by trained personnel. Quantitated neurologic deficit (ND) and brain histopathological examinations were developed. Fifteen minutes GBI resulted in rapid recovery within 12-24 hours PI without residual neurologic sequelae. Twenty minutes GBI caused severe neurologic deficit and within 4 days PI, a delayed Cushing response eventually leading to cardiac arrest. Sixteen minutes GBI resulted in severe neurologic deficit (monkeys unable to sit, stand, walk, or feed themselves), but with long term survival. Brain histopathological analyses revealed a combination of cortical and brainstem lesions. Severest changes were observed in the occipital (calcarine) cortex with less severe damage in the frontal and temporal regions. Oculomotor nuclei and medial longitudinal fasciculus in the midbrain were regularly affected. With this model we can test the efficacy of promising therapies in terms of clinically relevant variables.UNDERSTANDING the pathogenesis of postischemic (PI) encephalopathy and its amelioration by promising therapies has been hampered by the variability in degree of neurologic recovery 1 and brain histopathology 2 after seemingly comparable durations of global brain ischemia (GBI). Earlier studies suggested that 6 minutes GBI caused severe permanent brain damage*' 4 but recent studies indicate that the brain is capable of functional recovery after 20 1 and 60 minutes 6 of GBI. Data of past studies are difficult to interpret because recovery was evaluated in terms of acute physiological, biochemical or neuropathological changes not necessarily related to functional neurologic recovery 6 ' *• 7 and the methods for arresting brain circulation were highly invasive and probably contributed to PI morbidity and mortality. 1Using a simple, and noninvasive method for GBI in the rhesus monkey we determined the duration of ischemia resulting in severe ND with long-term PI survival. Our earlier observations in dogs in monkeys provided an estimate of the "threshold" of ischemic brain damage of 15 minutes. Sixteen minutes GBI resulted in severe neurologic deficit with survival, 15 minutes in complete recovery and 20 minutes in death within 7 days PI. Methods Anesthesia and Surgical PreparationsPrequarantined female rhesus monkeys 4 to 5 kg body weight (Primate Imports, Inc.) were fasted overnight with water ad libitum. Anesthesia was induced with 4% halothane (Fluothane, Ayerst, Inc.)/O 2 followed by intubation and IM injection of 0.4 mg atropine and .06 mg/kg pancuronium bromide and mechanical ventilation (Harvard Apparatus, Inc.) on 1% halothane/33% O 2 /66% N 2 O plus CO 2 to maintain end-tidal CO 2 (continuously monitored by an LB-1 Beckman infrared analyzer) at about 5-6%. ECG, rectal temperature, and urine output were continuously monitored and 5% dext...