NORMOXIC VENTILATION AFTER CARDIAC-ARREST REDUCES OXIDATION OF BRAIN LIPIDS AND IMPROVES NEUROLOGICAL OUTCOME

Background and Purpose-Increasing evidence that oxidative stress contr ibutes to delayed neuronal death after global cerebral ischemia has le d to reconsideration of the prolonged use of 100% ventilatory O-2 foll owing resuscitation from cardiac arrest. This study determined the tem poral course of oxidation of brain fatty acyl groups in a clinically r elevant canine model of cardiac arrest and resuscitation and tested th e hypothesis that postischemic ventilation with 21% inspired O-2, rath er than 100% O-2, results in reduced levels of oxidized brain lipids a nd decreased neurological impairment. Methods-Neurological deficit sco ring and high performance liquid chromatography measurement of fatty a cyl lipid oxidation were used in an established canine model using 10 minutes of cardiac arrest followed by resuscitation with different ven tilatory oxygenation protocols and restoration of spontaneous circulat ion for 30 minutes to 24 hours. Results-Significant increases in front al cortex lipid oxidation occurred after 10 minutes of cardiac arrest alone with no reperfusion and after reperfusion for 30 minutes, 2 hour s, 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 c hromatography/mass spectrometry as 13- and 9-hydroxyoctadecadienoic ac ids (13- and 9-HODE). Animals ventilated on 21% to 30% O-2 versus 100% O-2 for the first hour after resuscitation exhibited significantly lo wer levels of total and specific oxidized lipids in the frontal cortex (1.7+/-0.1 versus 3.12+/-0.78 mu g 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). Conclusions-With a clinically relevant canine m odel of 10 minutes of cardiac arrest, resuscitation with 21% versus 10 0% inspired O-2 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 guide lines that recommend the indiscriminate use of 100% ventilatory O-2 fo r undefined periods during and after resuscitation from cardiac arrest .