Lipid peroxidation as a cause of cerebral vasospasm.

In the present study, the vasocontractile activities of purified oxyhemoglobin, methemoglobin, peroxides of linoleic and arachidonic acid, and hydrogen peroxide were examined in vitro, using the canine basilar artery. It was shown that all of them possess a vasocontractile capacity in a dose-dependent fashion. Fresh canine arterial blood was incubated at 37 degree C for 2 weeks, and the daily change of its vasocontractile capacity and the amount of TBA-reactive substance was studied. This study revealed a gradual and parallel increase in both of them. In a clinical study with 32 SAH patients, the amount of TBA-reactive substance in the CSF was more elevated when angiographically confirmed vasospasm was present. The angiographical and histological responses of the basilar artery to the cisternal injection of 15-HPAA were studied in dogs. The cisternal injection of 15-HPAA (0.2 and 2.0 mg dissolved in bovine serum) caused a mild initial contraction of the basilar artery that lasted about 7 hours. On the third day, a stronger contraction occurred, persisting thereafter until sacrifice. Electronmicroscopy of those arterial samples revealed the disappearance of myofibrils, pyknotic changes of nuclei, and the appearance of vacuoles as well as electron-dense granules in the tunica media. The prolonged arterial contraction was always associated with remarkable destruction of the endothelial cells. These changes were essentially the same as those in experimental and clinical vasospasm. These data strongly indicate that free radical reactions initiated by clot lysis, represented by lipid peroxidation, plays an important role in the genesis of chronic vasospasm in subarachnoid hemorrhage.