Liu Y, Rosenthal R E, Haywood Y, Miljkovic-Lolic M, Vanderhoek J Y, Fiskum G
Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Stroke. 1998 Aug;29(8):1679-86. doi: 10.1161/01.str.29.8.1679.
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.
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.
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).
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.
越来越多的证据表明氧化应激导致全脑缺血后延迟性神经元死亡，这使得人们重新考虑在心脏骤停复苏后长时间使用100%通气氧。本研究确定了在与临床相关的心脏骤停和复苏犬模型中脑脂肪酰基氧化的时间进程，并检验了以下假设：缺血后吸入21%氧气而非100%氧气进行通气，可降低脑脂质氧化水平并减轻神经功能损害。
在一个既定的犬模型中，采用10分钟心脏骤停，随后用不同的通气氧合方案进行复苏，并恢复自主循环30分钟至24小时，运用神经功能缺损评分和高效液相色谱法测量脂肪酰脂质氧化。
仅心脏骤停10分钟且无再灌注时，以及再灌注30分钟、2小时和24小时后，额叶皮质脂质氧化显著增加（相对总235nm吸收峰面积分别为7.1±0.7SE、17.3±2.7、14.2±3.2、16.1±1.0和14.0±0.8；n = 4，P<0.05）。通过气相色谱/质谱法鉴定出主要的氧化脂质为13 - 和9 - 羟基十八碳二烯酸（13 - 和9 - HODE）。复苏后第一小时吸入21%至30%氧气而非100%氧气通气的动物，额叶皮质中总氧化脂质和特定氧化脂质水平显著较低（13 - HODE/g湿重皮质为1.7±0.1对3.12±0.78μg，n = 4至6，P<0.05），神经功能缺损评分也较低（45.1±3.6对58.3±3.8，n = 9，P<0.05）。
在一个与临床相关的10分钟心脏骤停犬模型中，吸入21%氧气与100%氧气进行复苏相比，可降低脑脂质氧化水平，并改善再灌注24小时后测得的神经功能结局。本研究进一步质疑了当前指南中推荐在心脏骤停复苏期间及之后无差别地长时间使用100%通气氧的合理性。
