Ann Thorac Surg 1996;62:1320
© 1996 The Society of Thoracic Surgeons
Discussion
Discussion
See also page 1313.
DR ANDREW S. WECHSLER (Richmond, VA): I was holding my breath waiting for the other shoe to drop and wondering whether you had tried this with NMDA receptor inhibitors. It is an interesting observation. What does this have to do with the neuroexcitatory damage that is seen? Did you try it with NOS inhibitors to determine whether or not by blocking NO production you could modulate the injury, or is that all for the future?
DR BROCK: We have performed preliminary experiments using both NMDA receptor inhibitors and NOS inhibitors, and in both cases have found histologic evidence that there is amelioration of neuroexcitatory damage. We are hoping to present these data very soon. As a brief preview I can tell you that the earliest histologic evidence of neuroexcitatoxicity after HCA seems to be apoptosis, and that this apoptosis appears to be blocked by NMDA antagonists and neuronal-specific nitric oxide inhibitors.
DR WECHSLER: Do you want to propose a mechanism for the injury?
DR BROCK: As a neurotransmitter, neuronal NO acts via the activation of guanylyl cyclase to form cyclic guanosine monophosphate. An increase in cyclic guanosine monophosphate activates other cellular processes and ultimately leads to the regulation of intracerebral blood flow. Besides its role as a mediator of physiologic functions in the brain, NO appears to act as a neurotoxin when it is produced in excess. There is an increasing body of evidence that NO neurotoxicity is mediated via a mechanism independent of its physiologic pathway through the generation of the oxidant peroxynitrite. Peroxynitrite-mediated injury probably is toxic to DNA directly.
Related Article
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Induction of Neuronal Nitric Oxide After Hypothermic Circulatory Arrest
- Malcolm V. Brock, Mary E. Blue, Charles J. Lowenstein, Frances A. Northington, Mary S. Lange, Michael V. Johnston, and William A. Baumgartner
Ann. Thorac. Surg. 1996 62: 1313-1320.
[Abstract]
[Full Text]
