Viability thresholds and the penumbra of focal ischemia
- 8 October 1994
- journal article
- review article
- Published by Wiley in Annals of Neurology
- Vol. 36 (4) , 557-565
- https://doi.org/10.1002/ana.410360404
Abstract
The classic concept of the viability thresholds of ischemia differentiates between two critical flow rates, the threshold of electrical failure and the threshold of membrane failure. These thresholds mark the upper and lower flow limits of the ischemic penumbra which is thought ot suffer only functional but not structural injury. Recent studies of the functional and metabolic disturbances suggest a more complex pattern of thresholds. At declining flow rates, protein synthesis is inhibited at first (at a threshold of about 0.55 ml/gm/min), followed by a stimulation of anaerobic glycolysis (at 0.35 ml/gm/min), the release of neurotransmitters and the beginning disturbance of energy metabolism (at about 0.20 ml/min), and finally the anoxic depolariztion (<0.15 ml/gm/min). The penumbra, as defined by the classic flow thresholds, does not remain viable for extended periods. Since viability of the tissue requires maintenance of energy‐dependent metabolic processes, penumbra is redefined as a region of constrained blood supply in which the energy metabolism is preserved. Imaging of the penumbra by combining autoradiographic cerebral blood flow measurements with bioluminescent images of adenosine triphosphate (ATP) demonstrates a gradual expansion of the infarct core (in which ATP is depleted) into the penumbra until, after a few hours, the penumbra has disappeared. It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply. This explains pharmacological suppression of periinfarct depolarizations lowering the threshold of metabolic disturbances and reducing the volume of the ischemic infarct.Keywords
This publication has 77 references indexed in Scilit:
- Repeated Negative DC Deflections in Rat Cortex following Middle Cerebral Artery Occlusion are Abolished by MK-801: Effect on Volume of Ischemic InjuryJournal of Cerebral Blood Flow & Metabolism, 1992
- The Effect of MK-801 on Cortical Spreading Depression in the Penumbral Zone following Focal Ischaemia in the RatJournal of Cerebral Blood Flow & Metabolism, 1992
- In vivo diffusion–perfusion magnetic resonance imaging of acute cerebral ischemiaCanadian Journal of Physiology and Pharmacology, 1991
- Ischemic Flow Threshold for Extracellular Glutamate Increase in Cat CortexJournal of Cerebral Blood Flow & Metabolism, 1989
- Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery OcclusionJournal of Cerebral Blood Flow & Metabolism, 1988
- Oxygen Extraction Fraction at Maximally Vasodilated Tissue in the Ischemic Brain Estimated from the Regional CO2 Responsiveness Measured by Positron Emission TomographyJournal of Cerebral Blood Flow & Metabolism, 1988
- Selective Gene Expression in Focal Cerebral IschemiaJournal of Cerebral Blood Flow & Metabolism, 1986
- Cortical Impedance and Extracellular Volume Changes following Middle Cerebral Artery Occlusion in CatsJournal of Cerebral Blood Flow & Metabolism, 1982
- Cerebral Glucose Utilization: Local Changes During and After Recovery from Spreading Cortical DepressionScience, 1979
- Correlation of Continuous Electroencephalograms With Cerebral Blood Flow Measurements During Carotid EndarterectomyStroke, 1973