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Glutamate excitotoxicity: A mechanism of neurologic injury associated with hypothermic circulatory arrest  J.M. Redmond, FRCSI (by invitation), A.M. Gillinov,

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Presentation on theme: "Glutamate excitotoxicity: A mechanism of neurologic injury associated with hypothermic circulatory arrest  J.M. Redmond, FRCSI (by invitation), A.M. Gillinov,"— Presentation transcript:

1 Glutamate excitotoxicity: A mechanism of neurologic injury associated with hypothermic circulatory arrest  J.M. Redmond, FRCSI (by invitation), A.M. Gillinov, MD (by invitation), K.J. Zehr, MD (by invitation), M.E. Blue, PhD (by invitation), J.C. Troncoso, MD (by invitation), B.A. Reitz, MD, D.E. Cameron, MD (by invitation), M.V. Johnston, MD (by invitation), W.A. Baumgartner, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 107, Issue 3, Pages (March 1994) DOI: /uri:pii:S Copyright © 1994 Mosby, Inc. Terms and Conditions

2 Fig. 1 Tympanic membrane temperatures during cooling, HCA, and rewarming. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

3 Fig. 2 Mean arterial pressure (MAP) versus time, before and after CPB.
The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

4 Fig. 3 Top, Arterial pH versus time, before and after CPB. Bottom, Arterial carbon dioxide tension (PaCO 2) versus time, before and after CPB. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

5 Fig. 4 Top, Blood hemoglobin (Hb) concentration versus time. Bottom, Blood glucose concentration versus time. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

6 Fig. 5 Tracings of the suppressive effect of dizocilpine on EEG activity in group A dogs. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

7 Fig. 6 Neurologic deficit score versus time. The neurologic recovery was significantly different between groups (p < by analysis of variance). The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

8 Fig. 7 Photomicrographs of histologic sections of CA1 hippocampus. A, Pyramidal cells of the CA1 hippocampus of a normal (negative control) dog are shown (one is marked with black arrow). B, Corresponding hippocampal cells of group B dogs are shrunken, angular, and hypereosinophilic, indicative of severe ischemic injury. C, In contrast, the hippocampal cells in the CA1 region of dogs treated with dizocilpine (group A) are well preserved. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

9 Fig. 7 Photomicrographs of histologic sections of CA1 hippocampus. A, Pyramidal cells of the CA1 hippocampus of a normal (negative control) dog are shown (one is marked with black arrow). B, Corresponding hippocampal cells of group B dogs are shrunken, angular, and hypereosinophilic, indicative of severe ischemic injury. C, In contrast, the hippocampal cells in the CA1 region of dogs treated with dizocilpine (group A) are well preserved. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

10 Fig. 7 Photomicrographs of histologic sections of CA1 hippocampus. A, Pyramidal cells of the CA1 hippocampus of a normal (negative control) dog are shown (one is marked with black arrow). B, Corresponding hippocampal cells of group B dogs are shrunken, angular, and hypereosinophilic, indicative of severe ischemic injury. C, In contrast, the hippocampal cells in the CA1 region of dogs treated with dizocilpine (group A) are well preserved. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

11 Fig. 8 NMDA-sensitive 3 H-glutamate binding in the CA1 hippocampus, zones 1 and 2 (CA1-1 and CA1-2) of group A, B, and C dogs. For group B dogs only, there was a significant decline in receptor density in CA1-2, compared with controls, group C. Receptor expression was preserved with dizocilpine treatment in group A in this zone. In CA1-1, with low NMDA receptor density, there was no significant reduction in binding in group B dogs. DPM, Discintillations per minute; NS, not significant. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

12 Fig. 9 NMDA binding in the CA3 hippocampus, zones 1 and 2 (CA3-1 and CA3-2). Significant reduction in binding occurred in group B dogs in CA3-2. Receptor expression was preserved in group A dogs in this zone. No significant reduction in binding occurred in either group in the CA3-1, where NMDA receptor density is low. DPM, Discintillations per minute; NS, not significant. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

13 Fig. 10 NMDA binding in the molecular layer (mol) of the dentate nucleus and molecular layer (mol) of the cerebellum. Significant reduction occurred in group B dogs only. DPM, Discintillations per minute. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

14 Fig. 11 AMPA binding in the CA1 hippocampus, zone 2 (CA1-2), the CA3 hippocampus, zone 2 (CA3-2), and the molecular layer (mol) of the dentate nucleus. Significant reduction in binding was observed in group B dogs only. DMP, Discintillations per minute. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

15 Fig. 12 Receptor autoradiograms demonstrating NMDA-sensitive 3 H-glutamate binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). Note the color scale for receptor density. Receptor density is diminished in group B dogs and preserved in group A dogs. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

16 Fig. 12 Receptor autoradiograms demonstrating NMDA-sensitive 3 H-glutamate binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). Note the color scale for receptor density. Receptor density is diminished in group B dogs and preserved in group A dogs. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

17 Fig. 12 Receptor autoradiograms demonstrating NMDA-sensitive 3 H-glutamate binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). Note the color scale for receptor density. Receptor density is diminished in group B dogs and preserved in group A dogs. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

18 Fig. 13 Receptor autoradiograms depicting AMPA binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). There is loss of receptor density in group B dogs in regions where NMDA receptor density is high. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

19 Fig. 13 Receptor autoradiograms depicting AMPA binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). There is loss of receptor density in group B dogs in regions where NMDA receptor density is high. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

20 Fig. 13 Receptor autoradiograms depicting AMPA binding in the hippocampus of group C dogs (top), group B dogs (middle), and group A dogs (bottom). There is loss of receptor density in group B dogs in regions where NMDA receptor density is high. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /uri:pii:S ) Copyright © 1994 Mosby, Inc. Terms and Conditions

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