Thresholds of focal cerebral ischemia in awake monkeys

Restricted access

✓ 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

Contributor Notes

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.
Headings
References
  • 1.

    Ames A IIIGurian BS: Effects of glucose and oxygen deprivation on function of isolated mammalian retina. J Neurophysiol 26:6176341963Ames A III Gurian BS: Effects of glucose and oxygen deprivation on function of isolated mammalian retina. J Neurophysiol 26:617–634 1963

    • Search Google Scholar
    • Export Citation
  • 2.

    Ames A IIIWright RLKowada Met al: Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol 52:4374531968Ames A III Wright RL Kowada M et al: Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol 52:437–453 1968

    • Search Google Scholar
    • Export Citation
  • 3.

    Astrup JSymon LBranston NMet al: Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8:51571977Astrup J Symon L Branston NM et al: Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8:51–57 1977

    • Search Google Scholar
    • Export Citation
  • 4.

    Aukland KBower BFBerliner RW: Measurement of local blood flow with hydrogen gas. Circ Res 14:1641871964Aukland K Bower BF Berliner RW: Measurement of local blood flow with hydrogen gas. Circ Res 14:164–187 1964

    • Search Google Scholar
    • Export Citation
  • 5.

    Colton T: Statistics in Medicine. Boston: Little, Brown and Co1974372 ppColton T: Statistics in Medicine. Boston: Little Brown and Co 1974 372 pp

    • Search Google Scholar
    • Export Citation
  • 6.

    Crowell RMOlsson YKlatzo Iet al: Temporary occlusion of the middle cerebral artery in the monkey: clinical and pathological observations. Stroke 1:4394481970Crowell RM Olsson Y Klatzo I et al: Temporary occlusion of the middle cerebral artery in the monkey: clinical and pathological observations. Stroke 1:439–448 1970

    • Search Google Scholar
    • Export Citation
  • 7.

    Denny-Brown DMeyer JS: The cerebral collateral circulation. 2. Production of cerebral infarction by ischemic anoxia and its reversibility in early stages. Neurology 7:5675791957Denny-Brown D Meyer JS: The cerebral collateral circulation. 2. Production of cerebral infarction by ischemic anoxia and its reversibility in early stages. Neurology 7:567–579 1957

    • Search Google Scholar
    • Export Citation
  • 8.

    Fein JMWillis JHamilton Jet al: Polarographical measurement of local cerebral blood flow in the conscious and anesthetized primate. Stroke 6:42511975Fein JM Willis J Hamilton J et al: Polarographical measurement of local cerebral blood flow in the conscious and anesthetized primate. Stroke 6:42–51 1975

    • Search Google Scholar
    • Export Citation
  • 9.

    Halsey JH JrCapra NFMcFarland RS: Use of hydrogen for measurement of regional cerebral blood flow. Problem of intercompartmental diffusion. Stroke 8:3513571977Halsey JH Jr Capra NF McFarland RS: Use of hydrogen for measurement of regional cerebral blood flow. Problem of intercompartmental diffusion. Stroke 8:351–357 1977

    • Search Google Scholar
    • Export Citation
  • 10.

    Hayakawa TWaltz AG: Changes of epidural pressures after experimental occlusion of one middle cerebral artery in cats. J Neurol Sci 26:3193331975Hayakawa T Waltz AG: Changes of epidural pressures after experimental occlusion of one middle cerebral artery in cats. J Neurol Sci 26:319–333 1975

    • Search Google Scholar
    • Export Citation
  • 11.

    Hayakawa TWaltz AG: Immediate effects of cerebral ischemia: evolution and resolution of neurological deficits after experimental occlusion of one middle cerebral artery in conscious cats. Stroke 6:3213271975Hayakawa T Waltz AG: Immediate effects of cerebral ischemia: evolution and resolution of neurological deficits after experimental occlusion of one middle cerebral artery in conscious cats. Stroke 6:321–327 1975

    • Search Google Scholar
    • Export Citation
  • 12.

    Heiss W-DHayakawa TWaltz AG: Cortical neuronal function during ischemia. Effects of occlusion of one middle cerebral artery on single-unit activity in cats. Arch Neurol 33:8138201976Heiss W-D Hayakawa T Waltz AG: Cortical neuronal function during ischemia. Effects of occlusion of one middle cerebral artery on single-unit activity in cats. Arch Neurol 33:813–820 1976

    • Search Google Scholar
    • Export Citation
  • 13.

    Hoff JTSmith ALHankinson HLet al: Barbiturate protection from cerebral infarction in primates. Stroke 6:28331975Hoff JT Smith AL Hankinson HL et al: Barbiturate protection from cerebral infarction in primates. Stroke 6:28–33 1975

    • Search Google Scholar
    • Export Citation
  • 14.

    Holbach K-HWassmann HHohelüchter KL: Reversibility of the chronic post-stroke state. Stroke 7:2963001976Holbach K-H Wassmann H Hohelüchter KL: Reversibility of the chronic post-stroke state. Stroke 7:296–300 1976

    • Search Google Scholar
    • Export Citation
  • 15.

    Hossmann K-AOlsson Y: Suppression and recovery of neuronal function in transient cerebral ischemia. Brain Res 22:3133251970Hossmann K-A Olsson Y: Suppression and recovery of neuronal function in transient cerebral ischemia. Brain Res 22:313–325 1970

    • Search Google Scholar
    • Export Citation
  • 16.

    Jones THMorawetz RBOjemann RGet al: Thresholds of focal cerebral ischemia in unanesthetized monkeys. Stroke 9:1011978 (Proceedings)Jones TH Morawetz RB Ojemann RG et al: Thresholds of focal cerebral ischemia in unanesthetized monkeys. Stroke 9:101 1978 (Proceedings)

    • Search Google Scholar
    • Export Citation
  • 17.

    Little JR: Implanted device for middle cerebral artery occlusion in conscious cats. Stroke 8:2582601977Little JR: Implanted device for middle cerebral artery occlusion in conscious cats. Stroke 8:258–260 1977

    • Search Google Scholar
    • Export Citation
  • 18.

    Michenfelder JDMilde JHSundt TM Jr: Cerebral protection by barbiturate anesthesia. Use after middle cerebral artery occlusion in Java monkeys. Arch Neurol 33:3453501976Michenfelder JD Milde JH Sundt TM Jr: Cerebral protection by barbiturate anesthesia. Use after middle cerebral artery occlusion in Java monkeys. Arch Neurol 33:345–350 1976

    • Search Google Scholar
    • Export Citation
  • 19.

    Molinari GFLaurent JP: A classification of experimental models of brain ischemia. Stroke 7:14171976Molinari GF Laurent JP: A classification of experimental models of brain ischemia. Stroke 7:14–17 1976

    • Search Google Scholar
    • Export Citation
  • 20.

    Morawetz RBDeGirolami UOjemann RGet al: Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 9:1431491978Morawetz RB DeGirolami U Ojemann RG et al: Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 9:143–149 1978

    • Search Google Scholar
    • Export Citation
  • 21.

    Ojemann RGCrowell RMRoberson GHet al: Surgical treatment of extracranial carotid occlusive disease. Clin Neurosurg 22:2142631974Ojemann RG Crowell RM Roberson GH et al: Surgical treatment of extracranial carotid occlusive disease. Clin Neurosurg 22:214–263 1974

    • Search Google Scholar
    • Export Citation
  • 22.

    Pasztor ESymon LDorsch NWCet al: The hydrogen clearance method in assessment of blood flow in cortex, white matter and deep nuclei of baboons. Stroke 4:5565671973Pasztor E Symon L Dorsch NWC et al: The hydrogen clearance method in assessment of blood flow in cortex white matter and deep nuclei of baboons. Stroke 4:556–567 1973

    • Search Google Scholar
    • Export Citation
  • 23.

    Sharbrough FWMessick JM JrSundt TM Jr: Correlation of continuous electrocephalograms with cerebral blood flow measurements during carotid endarterectomy. Stroke 4:6746831973Sharbrough FW Messick JM Jr Sundt TM Jr: Correlation of continuous electrocephalograms with cerebral blood flow measurements during carotid endarterectomy. Stroke 4:674–683 1973

    • Search Google Scholar
    • Export Citation
  • 24.

    Spetzler RFWeinstein PMehdorn M: New model for chronic reversible cerebral ischemia. Presented at the 46th Annual Meeting of the American Association of Neurological SurgeonsNew OrleansApril, 1978 (Paper No. 6)Spetzler RF Weinstein P Mehdorn M: New model for chronic reversible cerebral ischemia. Presented at the 46th Annual Meeting of the American Association of Neurological Surgeons New Orleans April 1978 (Paper No. 6)

    • Search Google Scholar
    • Export Citation
  • 25.

    Vander Eecken HMAdams RD: The anatomy and functional significance of the meningeal arterial anastomoses of the human brain. J Neuropathol Exp Neurol 12:1321571953Vander Eecken HM Adams RD: The anatomy and functional significance of the meningeal arterial anastomoses of the human brain. J Neuropathol Exp Neurol 12:132–157 1953

    • Search Google Scholar
    • Export Citation
  • 26.

    Willis JADoyle TFRamirez Aet al: A practical circuit for hydrogen clearance in blood flow measurement. TN 74-2. Washington, DC: Armed Forces Radiation Research Institute1974Willis JA Doyle TF Ramirez A et al: A practical circuit for hydrogen clearance in blood flow measurement. TN 74–2. Washington DC: Armed Forces Radiation Research Institute 1974

    • Search Google Scholar
    • Export Citation
  • 27.

    Yatsu FMDiamond IGraziano Cet al: Experimental brain ischemia: protection from irreversible damage with a rapid-acting barbiturate (methohexital). Stroke 3:7267321972Yatsu FM Diamond I Graziano C et al: Experimental brain ischemia: protection from irreversible damage with a rapid-acting barbiturate (methohexital). Stroke 3:726–732 1972

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 5472 4697 37
Full Text Views 3580 890 12
PDF Downloads 269 161 8
EPUB Downloads 0 0 0
PubMed
Google Scholar