BACKGROUND AND PURPOSE: Increasing 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. METHODS: Neurological 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. RESULTS: Significant 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 microg 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 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.
BACKGROUND AND PURPOSE: Increasing 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. METHODS:Neurological 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. RESULTS: Significant 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 microg 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 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.
Authors: Monica E Kleinman; Allan R de Caen; Leon Chameides; Dianne L Atkins; Robert A Berg; Marc D Berg; Farhan Bhanji; Dominique Biarent; Robert Bingham; Ashraf H Coovadia; Mary Fran Hazinski; Robert W Hickey; Vinay M Nadkarni; Amelia G Reis; Antonio Rodriguez-Nunez; James Tibballs; Arno L Zaritsky; David Zideman Journal: Circulation Date: 2010-10-19 Impact factor: 29.690
Authors: Monica E Kleinman; Allan R de Caen; Leon Chameides; Dianne L Atkins; Robert A Berg; Marc D Berg; Farhan Bhanji; Dominique Biarent; Robert Bingham; Ashraf H Coovadia; Mary Fran Hazinski; Robert W Hickey; Vinay M Nadkarni; Amelia G Reis; Antonio Rodriguez-Nunez; James Tibballs; Arno L Zaritsky; David Zideman Journal: Pediatrics Date: 2010-10-18 Impact factor: 7.124
Authors: Melika Hosseini; Robert H Wilson; Christian Crouzet; Arya Amirhekmat; Kevin S Wei; Yama Akbari Journal: Neurotherapeutics Date: 2020-04 Impact factor: 7.620
Authors: Viktoria Vereczki; Erica Martin; Robert E Rosenthal; Patrick R Hof; Gloria E Hoffman; Gary Fiskum Journal: J Cereb Blood Flow Metab Date: 2006-06 Impact factor: 6.200
Authors: Gary Fiskum; Camelia A Danilov; Zara Mehrabian; Linda L Bambrick; Tibor Kristian; Mary C McKenna; Irene Hopkins; E M Richards; Robert E Rosenthal Journal: Ann N Y Acad Sci Date: 2008-12 Impact factor: 5.691
Authors: Julie L Hazelton; Irina Balan; Greg I Elmer; Tibor Kristian; Robert E Rosenthal; Gary Krause; Thomas H Sanderson; Gary Fiskum Journal: J Neurotrauma Date: 2010-04 Impact factor: 5.269