Document Detail

Effect of excitatory amino acid receptor blocker MK-801 on overall, neurologic, and morphologic outcome after prolonged cardiac arrest in dogs.
MedLine Citation:
PMID:  2556064     Owner:  NLM     Status:  MEDLINE    
Excitatory amino acids accumulating in the brain during ischemia may cause selective neuronal damage postischemia. This hypothesis was tested in a series of studies using MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in a reproducible outcome model of prolonged cardiac arrest in dogs. After normothermic ventricular fibrillation cardiac arrest, the dogs were resuscitated with closed-chest femoral veno-arterial cardiopulmonary bypass. At 4 h they were separated from bypass, ventilation was controlled for 20 h, and intensive care was continued to 96 h. In Study I, ventricular fibrilation cardiac arrest (no-flow) was 17 min; starting immediately with reperfusion, MK-801 1200 mg/kg (n = 5) or an equal volume of placebo (n = 5) was infused over 12 h in blinded, randomized fashion. In Study II, the duration of the no-flow period was reduced to 15 min, and MK-801 2400 (n = 4) or placebo (n = 4) was infused. In Study III, no-flow lasted for 15 min, and MK-801 2400 mg/kg was started 30 min before ventricular fibrillation (n = 4); comparison was with Study II controls. In all three studies, MK-801 plasma concentrations peaked at greater than 50 ng/ml and were 15-30 ng/ml over 12 h. All 22 dogs of experiments within protocol survived with severe brain damage. MK-801 delayed return of pupillary reactivity, EEG activity, consciousness, and respiration, necessitating longer periods of controlled ventilation. Neurologic deficit scores, overall performance categories, and brain and heart morphologic damage scores at 96 h did not differ between placebo and MK-801 pretreatment or post-treatment groups. These negative outcome results after prolonged cardiac arrest do not negate the hyperexcitability hypothesis of selective vulnerability, but suggest the existance of additional mechanisms of secondary brain damage.
F Sterz; Y Leonov; P Safar; A Radovsky; S W Stezoski; H Reich; G T Shearman; T F Greber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  71     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1989 Dec 
Date Detail:
Created Date:  1990-01-02     Completed Date:  1990-01-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  907-18     Citation Subset:  AIM; IM    
Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh, Pennsylvania.
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MeSH Terms
Anticonvulsants / therapeutic use
Dibenzocycloheptenes / therapeutic use*
Dizocilpine Maleate
Heart Arrest / therapy*
Receptors, N-Methyl-D-Aspartate
Receptors, Neurotransmitter / antagonists & inhibitors*
Time Factors
Grant Support
Reg. No./Substance:
0/Anticonvulsants; 0/Dibenzocycloheptenes; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Neurotransmitter; 77086-22-7/Dizocilpine Maleate

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