Current concepts of pathophysiology and management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Approximately 10 in 100,000 persons suffer rupture of a saccular intracranial aneurysm annually, and roughly 60% of these will survive the initial catastrophe in reasonable neurological condition. Of the many ensuing complications of aneurysmal subarachnoid hemorrhage, the most frustrating continues to be a form of delayed-onset cerebral arterial narrowing known as vasospasm. Because it is caused by thick subarachnoid blood clots coating the adventitial surface of cerebral arteries, the distribution and severity of vasospasm correlates closely with location and volume of subarachnoid hematoma as visualized on computed tomography (CT). Critical vasospasm causes cerebral ischemia and infarction: the "second stroke." It is now know that vasospasm represents sustained arterial contraction rather than structural thickening of the vessel wall with lumen encroachment. A large body of evidence points to oxyhemoglobin, released from lysing erythrocytes, as the principal component of blood clot responsible for this contraction. The precise mechanism by which oxyhemoglobin causes prolonged vascular smooth muscle cell constriction has not yet been established, but possibilities include secondary generation of vasoactive free radicals, lipid peroxides, eicosanoids, bilirubin, and endothelin. Vasospasm treatments are directed at preventing or reversing arterial narrowing, or at preventing or reversing cerebral ischemia. Several treatments from the latter category, namely, hypertensive, hypervolemic hemodilutional therapy and the calcium channel blocker nimodipine, have proven moderately effective and are in widespread clinical use. It has also been possible to mechanically dilate vasospastic vessels with transluminal angioplasty improving cerebral blood flow to ischemic brain. However we are still in need of an effective agent to prevent arterial narrowing, and several hopeful candidates in this category of treatment are clot lytic agent tissue plasminogen activator (rt-PA) and an inhibitor of iron-dependent peroxidation, 21-aminosteroid U74006F (tirilazad mesylate).