From the Department of Biochemistry and Molecular Biology (Y.L., R.E.R.,
J.Y.V.) and the Department of Emergency Medicine (R.E.R., J.H., M.M.-L.), The
George Washington University School of Medicine and Health Sciences,
Washington, DC, and the Department of Anesthesiology (G.F.), University of
Maryland Baltimore School of Medicine.
Correspondence to Dr Gary Fiskum, Department of Anesthesiology, University of Maryland Baltimore School of Medicine, Baltimore, MD 21201. E-mail gfiskum{at}anesthlab.ab.umd.edu
Background and
PurposeIncreasing evidence that oxidative stress contributes to
delayed neuronal death after global cerebral ischemia has led
to reconsideration of the prolonged use of 100% ventilatory
O2 following resuscitation from cardiac arrest. This study
determined the temporal course of oxidation of brain fatty acyl groups
in a clinically relevant canine model of cardiac arrest and
resuscitation and tested the hypothesis that postischemic
ventilation with 21% inspired O2, rather than 100%
O2, results in reduced levels of oxidized brain lipids and
decreased neurological impairment.
MethodsNeurological deficit scoring and high
performance liquid chromatography measurement
of fatty acyl lipid oxidation were used in an established canine model
using 10 minutes of cardiac arrest followed by resuscitation with
different ventilatory oxygenation protocols and
restoration of spontaneous circulation for 30 minutes to 24 hours.
ResultsSignificant increases in frontal cortex lipid oxidation
occurred after 10 minutes of cardiac arrest alone with no reperfusion
and after reperfusion for 30 minutes, 2 hours, and 24 hours (relative
total 235-nm absorbing peak areas=7.1±0.7 SE, 17.3±2.7, 14.2±3.2,
16.1±1.0, and 14.0±0.8, respectively; n=4, P<0.05).
The predominant oxidized lipids were identified by gas
chromatography/mass spectrometry as 13- and
9-hydroxyoctadecadienoic acids (13- and 9-HODE). Animals ventilated on
21% to 30% O2 versus 100% O2 for the first
hour after resuscitation exhibited significantly lower levels of total
and specific oxidized lipids in the frontal cortex (1.7±0.1 versus
3.12±0.78 µg 13-HODE/g wet wt cortex., n=4 to 6,
P<0.05) and lower neurological deficit scores
(45.1±3.6 versus 58.3±3.8, n=9, P<0.05).
ConclusionsWith a clinically relevant canine model of 10 minutes
of cardiac arrest, resuscitation with 21% versus 100% inspired
O2 resulted in lower levels of oxidized brain lipids and
improved neurological outcome measured after 24 hours of reperfusion.
This study casts further doubt on the appropriateness of present
guidelines that recommend the indiscriminate use of 100% ventilatory
O2 for undefined periods during and after resuscitation
from cardiac arrest.
Anesthesiology/Critical
Care Medicine,
The Johns Hopkins University,
School of Medicine,
Baltimore, Maryland
© 1998 American Heart Association, Inc.
Original Contributions
Normoxic Ventilation After Cardiac Arrest Reduces Oxidation of Brain Lipids and Improves Neurological Outcome
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