Abstract
It is well known that oxyhemoglobin in its autoxidation to methemoglobin produces active species of oxygens (O·-2, H2O2, OH·, 1O2), which in turn generate toxic free radical reactions, such as peroxidation of polyunsaturated fatty acids in the biomembrane. Since active species of oxygen and lipid hydroperoxides possess tissue toxicity, it is easy to speculate that they play some role in the production of chronic cerebral vasospasm. Based on this assumption, experimental as well as clinical studies were carried out.
Fresh arterial blood of a dog was incubated at 37°C for 14 days and the daily change of its peroxide value in each sample by thiobarbituric acid test was measured. To follow the conversion of oxyhemoglobin to methemoglobin, the spectrophotometric absorbance curve of each sample was traced. The peroxide value of the supernatant of each sample was initially low and gradually increased to reach a plateau in 3 to 5 days. This high level of the peroxide value was maintained thereafter. By the analysis of the spectrophotometric absorbance curves, it was confirmed that the conversion of oxyhemoglobin to methemoglobin occurred in parallel with the increase of peroxide value.
For the purpose of verifying the tissue toxicity of lipid hydroperoxide to the cerebral vessels, 15-hydroperoxy arachidonic acid was injected into the subarachnoid space of dogs and the histological change of the basilar artery was examined by electron microscope. Myonecrotic changes were observed in the canine basilar artery after intracisternal injection of 15-hydroperoxy arachidonic acid.
With 25 patients sustaining SAH due to rupture of an intracranial aneurysm, peroxide content of lumbar CSF was studied to examine the correlation between the peroxide formation and the occurrence of vasospasm. The peroxide values in patients with vasospasm were higher than those without vasospasm. As to the time course of peroxide value, a statistically significant difference (p<0.01) between the groups with and without vasospasm was revealed in I to 3rd and 7 to 9th days after the onset of SAH. These data strongly suggest that free radical reactions initiated by clot lysis play a significant role in the genesis of vasospasm.
