缺氧、高氧、局部缺血和脑坏死。

Hypoxia, hyperoxia, ischemia, and brain necrosis.

作者信息

Miyamoto O, Auer R N

机构信息

Department of Basic Sports Medicine, Kagawa Medical University, Japan.

出版信息

Neurology. 2000 Jan 25;54(2):362-71. doi: 10.1212/wnl.54.2.362.

DOI:10.1212/wnl.54.2.362

PMID:10668697

Abstract

BACKGROUND

Human brains show widespread necrosis when death occurs after coma due to cardiac arrest, but not after hypoxic coma. It is unclear whether hypoxia alone can cause brain damage without ischemia. The relationship of blood oxygenation and vascular occlusion to brain necrosis is also incompletely defined.

METHODS

We used physiologically monitored Wistar rats to explore the relationship among arterial blood oxygen levels, ischemia, and brain necrosis. Hypoxia alone (PaO2 = 25 mm Hg), even at a blood pressure (BP) of 30 mm Hg for 15 minutes, yielded no necrotic neurons. Ischemia alone (unilateral carotid ligation) caused necrosis in 4 of 12 rats, despite a PaO2 > 100 mm Hg. To reveal interactive effects of hypoxia and ischemia, groups were studied with finely graded levels of hypoxia at a fixed BP, and with controlled variation in BP at fixed PaO2. In separate series, focal ischemic stroke was mimicked with transient middle cerebral artery (MCA) occlusion, and the effect of low, normal, and high PaO2 was studied.

RESULTS

Quantitated neuropathology worsened with every 10 mm Hg decrement in BP, but the effect of altering PaO2 by 10 mm Hg was not as great, nor as consistent. Autoradiographic study of cerebral blood flow with 14C-iodoantipyrine revealed no hypoxic vasodilatation during ischemia. In the MCA occlusion model, milder hypoxia than in the first series (PaO2 = 46.5 +/- 1.4 mm Hg) exacerbated necrosis to 24.3 +/- 4.7% of the hemisphere from 16.6 +/- 7.0% with normoxia (PaO2 = 120.5 +/- 4.1 mm Hg), whereas hyperoxia (PaO2 = 213.9 +/- 5.8 mm Hg) mitigated hemispheric damage to 7.50 +/- 1.86%. Cortical damage was strikingly sensitive to arterial PaO2, being 12.8 +/- 3.1% of the hemisphere with hypoxia, 7.97 +/-4.63% with normoxia, and only 0.3 +/- 0.2% of the hemisphere with hyperoxia (p < 0.01), and necrosis being eliminated completely in 8 of 10 animals.

CONCLUSIONS

Hypoxia without ischemia does not cause brain necrosis but hypoxia exacerbates ischemic necrosis. Hyperoxia potently mitigates brain damage in this MCA occlusion model, especially in neocortex.

摘要

背景

心脏骤停导致昏迷后死亡时，人类大脑会出现广泛坏死，但缺氧性昏迷后则不会。目前尚不清楚单纯缺氧是否能在无缺血的情况下导致脑损伤。血液氧合与血管阻塞和脑坏死之间的关系也尚未完全明确。

方法

我们使用生理监测的Wistar大鼠来探究动脉血氧水平、缺血和脑坏死之间的关系。单纯缺氧（动脉血氧分压[PaO2]=25mmHg），即使血压（BP）为30mmHg持续15分钟，也未产生坏死神经元。单纯缺血（单侧颈动脉结扎）在12只大鼠中有4只导致坏死，尽管PaO2>100mmHg。为揭示缺氧和缺血的交互作用，研究了在固定血压下具有精细分级缺氧水平的组，以及在固定PaO2下血压的可控变化。在单独的系列中，用短暂性大脑中动脉（MCA）闭塞模拟局灶性缺血性中风，并研究低、正常和高PaO2的影响。

结果

定量神经病理学随着血压每降低10mmHg而恶化，但将PaO2改变10mmHg的影响没有那么大，也不那么一致。用14C-碘安替比林进行脑血流的放射自显影研究显示，缺血期间没有缺氧性血管扩张。在MCA闭塞模型中，比第一个系列中更轻度的缺氧（PaO2=46.5±1.4mmHg）使坏死从正常氧合（PaO₂=120.5±4.1mmHg）时的半球的16.6±7.0%加剧到24.3±4.7%，而高氧（PaO2=213.9±5.8mmHg）将半球损伤减轻到7.50±1.86%。皮质损伤对动脉PaO2极为敏感，缺氧时为半球的12.8±3.1%，正常氧合时为7.97±4.63%，高氧时仅为半球的0.3±0.2%（p<0.01），并且10只动物中有8只完全消除了坏死。