TY - JOUR
T1 - Pathophysiology of cerebral injury and future management
AU - Baumgartner, William A.
AU - Redmond, Mark
AU - Brock, Malcolm
AU - Tseng, Elaine
AU - Blue, Mary E.
AU - Troncoso, Juan C.
AU - Johnston, Michael V.
N1 - Copyright:
Copyright 2006 Elsevier B.V., All rights reserved.
PY - 1997/3
Y1 - 1997/3
N2 - Central nervous system dysfunction continues to represent significant morbidity and associated mortality in patients undergoing cardiac surgery. Neurological dysfunction is most exaggerated in patients undergoing hypothermic circulatory arrest (HCA). Although surgical techniques, anesthetic management, and postoperative care have significantly improved over the past two decades, the incidence of stroke and other neurocognitive deficits remains problematic. Understanding the mechanisms of cell death associated with HCA may provide information that is germane to all types of cerebral injury involved in cardiac surgery. Using a closed-chest cardiopulmonary bypass model, dogs underwent 2 hours of circulatory arrest at 18°C followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis and receptor autoradiography for NMDA glutamate receptor subtype expression. Using a selective NMDA (-glutamate) receptor antagonist (MK801), an AMPA-antagonist (NBQX) and a nonspecific neuroprotectant (GM1-ganglioside), the role of glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. Using a similar canine preparation, a microdialysis technique was used to evaluate the role of nitric oxide in neuronal death. Arginine plus oxygen is converted to nitric oxide plus citrulline by the action of nitric oxide synthase. Simultaneous infusion of artificial cerebrospinal fluid containing L-[14C] arginine or L-[14C] arginine and L-NAME (a nitric oxide synthase inhibitor) was performed in contralateral hemispheres. Citrulline recovery in the cerebrospinal fluid, citrulline production in vitro from canine cortical homogenates, and nitric oxide metabolites in the serum were all significantly increased during HCA and reperfusion. These studies demonstrated that neurotoxicity following HCA involves a significant and early induction of neuronal NOS expression and neuronal processes leading to widespread augmented NO production in the brain. Continued research into the pathophysiologic mechanisms involved in cerebral injury will undoubtedly yield a safe and reliable neuroprotectant strategy.
AB - Central nervous system dysfunction continues to represent significant morbidity and associated mortality in patients undergoing cardiac surgery. Neurological dysfunction is most exaggerated in patients undergoing hypothermic circulatory arrest (HCA). Although surgical techniques, anesthetic management, and postoperative care have significantly improved over the past two decades, the incidence of stroke and other neurocognitive deficits remains problematic. Understanding the mechanisms of cell death associated with HCA may provide information that is germane to all types of cerebral injury involved in cardiac surgery. Using a closed-chest cardiopulmonary bypass model, dogs underwent 2 hours of circulatory arrest at 18°C followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis and receptor autoradiography for NMDA glutamate receptor subtype expression. Using a selective NMDA (-glutamate) receptor antagonist (MK801), an AMPA-antagonist (NBQX) and a nonspecific neuroprotectant (GM1-ganglioside), the role of glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. Using a similar canine preparation, a microdialysis technique was used to evaluate the role of nitric oxide in neuronal death. Arginine plus oxygen is converted to nitric oxide plus citrulline by the action of nitric oxide synthase. Simultaneous infusion of artificial cerebrospinal fluid containing L-[14C] arginine or L-[14C] arginine and L-NAME (a nitric oxide synthase inhibitor) was performed in contralateral hemispheres. Citrulline recovery in the cerebrospinal fluid, citrulline production in vitro from canine cortical homogenates, and nitric oxide metabolites in the serum were all significantly increased during HCA and reperfusion. These studies demonstrated that neurotoxicity following HCA involves a significant and early induction of neuronal NOS expression and neuronal processes leading to widespread augmented NO production in the brain. Continued research into the pathophysiologic mechanisms involved in cerebral injury will undoubtedly yield a safe and reliable neuroprotectant strategy.
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M3 - Article
C2 - 9271760
AN - SCOPUS:0030865794
SN - 0886-0440
VL - 12
SP - 300
EP - 311
JO - Journal of Cardiac Surgery
JF - Journal of Cardiac Surgery
IS - 2 SUPPL. 1
ER -