Hypoxia, hyperoxia, ischemia, and brain necrosis

Background: Human brains show widespread necrosis when death occurs after c oma due to cardiac arrest, but not after hypoxic coma. It is unclear whethe r hypoxia alone can cause brain damage without ischemia. The relationship o f blood oxygenation and vascular occlusion to brain necrosis is also incomp letely defined. Methods: We used physiologically monitored Wistar rats to e xplore the relationship among arterial blood oxygen levels, ischemia, and b rain necrosis. Hypoxia alone (PaO2 = 25 mm Hg), even at a blood pressure (B P) 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 Pa O2 > 100 mm Hg. To reveal interactive effects of hypoxia and ischemia, grou ps were studied with finely graded levels of hypoxia at a fixed BP, and wit h controlled variation in BP at fixed PaO2. In separate series, focal ische mic stroke was mimicked with transient middle cerebral artery (MCA) occlusi on, and the effect of low, normal, and high PaO2 was studied. Results: Quan titated neuropathology worsened with every 10 mm Hg decrement in BP, but th e effect of altering PaO2 by 10 mm Hg was not as great, nor as consistent. Autoradiographic study of cerebral blood flow with C-14-iodoantipyrine reve aled no hypoxic vasodilatation during ischemia. In the MCA occlusion model, milder hypoxia than in the first series (PaO2 = 46.5 +/- 1.4 mm Hg) exacer bated necrosis to 24.3 +/- 4.7% of the hemisphere from 16.6 +/- 7.0% with n ormoxia (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 w as strikingly sensitive to arterial PaO2, being 12.8 +/- 3.1% of the hemisp here with hypoxia, 7.97 +/- 4.63% with normoxia, and only 0.3 +/- 0.2% of t he hemisphere with hyperoxia (p < 0.01), and necrosis being eliminated comp letely in 8 of 10 animals. Conclusions: Hypoxia without ischemia does not c ause brain necrosis but hypoxia exacerbates ischemic necrosis. Hyperoxia po tently mitigates brain damage in this MCA occlusion model, Especially in ne ocortex.