Abstract 16029: Increased Brain Injury After Asphyxial Cardiac Arrest vs. Ventricular Fibrillation is Associated With Greater Brain Antioxidant Depletion
Background: Cardiac arrest may present as ventricular fibrillation (VF) or asphyxia (ACA). Differences in outcomes between VF and ACA are recognized but treatment remains static. ACA has been linked with poor neurological outcomes though the mechanisms for these differences are unknown.
Hypothesis: ACA results in greater reactive oxygen species (ROS) generation on reperfusion accounting for increased brain injury compared to VF.
Methods: Isoflurane-anesthetized male Sprague-Dawley rats (n=24, 3 shams) were subjected to 5 minute no flow VF or ACA. Resuscitation was attempted using CPR, epinephrine, bicarbonate, and defibrillation (VF only). At 15 minutes post-ROSC, brain ascorbate was assessed fluorometrically with 4-((9-acridinecarbonyl)-amino)-2,2,6,6-tetramethylpiperidine-1-oxyl radical (Ac-TEMPO).Total antioxidant reserve of the samples was assessed with 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) and luminol. Hippocampal neuronal loss and recall of cue conditioned fear (measured as freezing %) were assessed at day 7. Comparisons were made to sham and data were analyzed using ANOVA or Kruskal-Wallis test.
Results: Ascorbate concentrations (mean [nmol/mg protein]; 95% CI) in the rat brain was significantly different between groups (p=0.0004). Non-arrested shams had higher levels (39.1; 37.0-41.3) followed by VF (31.7; 29.6-33.8), then ACA (28.4; 25.6-31.3). ACA brain ascorbate was significantly reduced compared to VF brain ascorbate. Total antioxidant reserve of the same brain samples were congruous (p=0.0001): There was a significant decrease in recall of cued conditioned fear in ACA vs. VF (p<0.05) and significantly greater hippocampal neuronal loss (p<0.001, live cells/mm CA1) in ACA (3.99; 2.4-5.6) vs. VF (10.35; 7.2-13.5).
Conclusions: ACA results in greater ROS generation as marked by antioxidant depletion which may explain worsened outcomes despite similar no flow ischemic durations.
Author Disclosures: A.M. Lamade: None. T. Uray: None. E. Kenny: None. A. Misse: None. J. Stezoski: None. T. Drabek: None. P. Kochanek: None. C. Dezfulian: Consultant/Advisory Board; Modest; Ikaria/Mallinkrodt.
- © 2015 by American Heart Association, Inc.