New Evidence Pointing to Oxyhemoglobin as the Cause of Vasospasm

Experiments were conducted in monkeys to determine which substances in blood may cause cerebral vasospasm following subarachnoid hemorrhage (SAH), and to examine the mechanism of action of these substances. In the first experiment, monkeys were given intrathecal injections, twice a day for 6 days, with one of the following solutions: mock cerebrospinal fluid (CSF); oxyhemoglobin (OxyHb); methemoglobin; bilirubin; supernatant fluid from an incubated mixture of autologous blood and mock CSF (n = 8 in each group). Comparison of cerebral angiograms taken before and after the injections showed significant vasospasm only in the groups which had received OxyHb and supernatant fluid (mean reduction in middle cerebral artery diameter, 27% ± 5% and 26% ± 7%, p < 0.05, respectively). These data suggest that OxyHb is an important cause of cerebral vasospasm following SAH. In the second experiment, monkeys were randomly assigned to have subarachnoid placement of one of the following: agarose gel alone (n = 2); agarose plus OxyHb (n = 3); agarose plus OxyHb plus intrathecal administration of superoxide dismutase and catalase (n = 6); agarose plus OxyHb plus intrathecal administration of placebo (n = 6). Vasospasm was assessed by comparing angiograms taken before and 7 days after placement of subarachnoid compounds. Agarose-OxyHb gel alone caused significant reduction in middle cerebral artery diameter (41% ± 8%, p < 0.005, paired t-test) which was associated with ultrastructural damage to smooth muscle. Treatment with superoxide dismutase plus catalase or with placebo attenuated vasospasm, although significant narrowing persisted in both groups (27% ± 12% and 26% ± 13%, p < 0.05, paired t-test, respectively). The failure of superoxide dismutase and catalase to prevent OxyHb-induced vasospasm suggests free-radical mediated mechanisms may not be important in its genesis. However, only one combination of doses of enzymes was administered and other dose schedules might be efficacious.