title: Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome.
abstract: Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, PA 15260.
authors.forename: P
authors.initials: P
authors.lastname: Vaagenes
authors.forename: P
authors.initials: P
authors.lastname: Safar
authors.forename: W
authors.initials: W
authors.lastname: Diven
authors.forename: J
authors.initials: J
authors.lastname: Moossy
authors.forename: G
authors.initials: G
authors.lastname: Rao
authors.forename: R
authors.initials: R
authors.lastname: Cantadore
authors.forename: S
authors.initials: S
authors.lastname: Kelsey
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D003402:Creatine Kinase / Q000134:cerebrospinal fluid; D004285:Dogs; D006323:Heart Arrest / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes; D007773:Lactates / Q000134:cerebrospinal fluid; D012151:Resuscitation
chemical_list: D007527:Isoenzymes; D007773:Lactates; D003402:Creatine Kinase