Intracranial heme metabolism and cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Background and Purpose - The goal of this prospective study was to clarify the potential role of an inducible heme- metabolizing enzyme, heme oxygenase ( HO)- 1, and an inducible iron- detoxifying protein, ferritin, in cerebral vasospasm after aneurysmal subarachnoid hemorrhage ( SAH). Methods - The authors measured the levels of bilirubin and iron, which are by- products of HO- 1, and the ferritin levels in the cerebrospinal fluid in 39 consecutive patients with aneurysmal SAH of Fisher computed tomography group III, and determined the relationship between these by- products of HO- 1 or ferritin and vasospasm. Results - Fourteen of 39 patients ( 35.9%) developed asymptomatic vasospasm, while 6 patients ( 15.4%) developed symptomatic vasospasm. The levels of ferritin, bilirubin, and iron were all significantly elevated after SAH. The levels of ferritin and bilirubin were significantly higher in patients with no vasospasm than in patients with asymptomatic and symptomatic vasospasm on days 5 through 7 ( P < 0.05, respectively) and on days 11 through 14 ( P < 0.025 in bilirubin) after SAH. However, no significant difference was observed in the iron levels between these patient groups. Conclusions - This is the first study to show that higher levels of bilirubin and ferritin in the cerebrospinal fluid after SAH were associated with no vasospasm in clinical settings. These findings support the concept that the induction of HO- 1 and ferritin may be an intrinsic regulatory mechanism that acts against cerebral vasospasm.