Department of Critical Care Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Crit Care Med. 2011 Feb;39(2):335-43. doi: 10.1097/CCM.0b013e3181ffda0e.
To determine the effects of normoxic vs. hyperoxic resuscitation on oxidative stress in a model of pediatric asphyxial cardiac arrest.
Prospective, interventional study.
University research laboratory.
Postnatal day 16-18 rats (n = 5 per group).
Rats underwent asphyxial cardiac arrest for 9 min. Rats were randomized to receive 100% oxygen, room air, or 100% oxygen with polynitroxyl albumin (10 mL·kg⁻¹ intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation. Shams recovered in 100% oxygen or room air after surgery.
Physiological variables were recorded at baseline to 1 hr after resuscitation. At 6 hrs after asphyxial cardiac arrest, levels of reduced glutathione and protein-thiols (fluorescent assay), activities of total superoxide dismutase and mitochondrial manganese superoxide dismutase (cytochrome c reduction method), manganese superoxide dismutase expression (Western blot), and lipid peroxidation (4-hydroxynonenal Michael adducts) were evaluated in brain tissue homogenates. Hippocampal 3-nitrotyrosine levels were determined by immunohistochemistry 72 hrs after asphyxial cardiac arrest. Survival did not differ among groups. At 1 hr after resuscitation, Pao2, pH, and mean arterial pressure were decreased in room air vs. 100% oxygen rats (59 ± 3 vs. 465 ± 46 mm Hg, 7.36 ± 0.05 vs. 7.42 ± 0.03, 35 ± 4 vs. 45 ± 5 mm Hg; p < .05). Rats resuscitated with 100% oxygen had decreased hippocampal reduced glutathione levels vs. sham (15.3 ± 0.4 vs. 20.9 ± 4.1 nmol·mg protein⁻¹; p < .01). Hippocampal manganese superoxide dismutase activity was significantly increased in 100% oxygen rats vs. sham (14 ± 2.4 vs. 9.5 ± 1.6 units·mg protein⁻¹, p < .01), with no difference in protein expression of manganese superoxide dismutase. Room air and 100% oxygen plus polynitroxyl albumin groups had hippocampal reduced glutathione and manganese superoxide dismutase activity levels comparable with sham. Protein thiol levels were unchanged across groups. Compared with all other groups, rats receiving 100% oxygen had increased immunopositivity for 3-nitrotyrosine in the hippocampus and increased lipid peroxidation in the cortex.
Resuscitation with 100% oxygen leads to increased oxidative stress in a model that mimics pediatric cardiac arrest. This may be prevented by using room air or giving an antioxidant with 100% oxygen resuscitation.
在小儿窒息性心跳骤停模型中，确定常氧与高氧复苏对氧化应激的影响。
前瞻性、干预性研究。
大学研究实验室。
出生后 16-18 天的大鼠（每组 5 只）。
大鼠经历 9 分钟的窒息性心跳骤停。大鼠随机接受 100%氧气、空气或 100%氧气加多聚硝叉白蛋白（复苏开始后 0 和 30 分钟时各 10 mL·kg⁻¹ 静脉注射）1 小时。假手术组大鼠在手术后于 100%氧气或空气恢复。
在复苏后 1 小时内记录生理变量。在窒息性心跳骤停后 6 小时，评估脑匀浆中还原型谷胱甘肽和蛋白巯基（荧光测定法）、总超氧化物歧化酶和线粒体锰超氧化物歧化酶的活性（细胞色素 c 还原法）、锰超氧化物歧化酶的表达（Western blot）和脂质过氧化（4-羟基壬烯醛迈克尔加合物）。72 小时后通过免疫组化测定海马体 3-硝基酪氨酸水平。各组间存活率无差异。复苏 1 小时后，空气组大鼠的 PaO2、pH 和平均动脉压较 100%氧气组降低（59 ± 3 对 465 ± 46 mm Hg、7.36 ± 0.05 对 7.42 ± 0.03、35 ± 4 对 45 ± 5 mm Hg；p <.05）。与假手术组相比，100%氧气复苏组大鼠的海马体还原型谷胱甘肽水平降低（15.3 ± 0.4 对 20.9 ± 4.1 nmol·mg 蛋白⁻¹；p <.01）。100%氧气组大鼠的海马体锰超氧化物歧化酶活性明显高于假手术组（14 ± 2.4 对 9.5 ± 1.6 单位·mg 蛋白⁻¹，p <.01），但锰超氧化物歧化酶的蛋白表达无差异。空气组和 100%氧气加多聚硝叉白蛋白组的海马体还原型谷胱甘肽和锰超氧化物歧化酶活性水平与假手术组相当。蛋白巯基水平在各组间无变化。与其他所有组相比，接受 100%氧气的大鼠海马体 3-硝基酪氨酸免疫阳性反应增加，皮质脂质过氧化增加。
在模拟小儿心跳骤停的模型中，100%氧气复苏可导致氧化应激增加。使用空气或在 100%氧气复苏时给予抗氧化剂可能会预防这种情况。
