Endothelial-derived relaxation factor nitric oxide (NO) was shown to mediate autoregulation and chemoregulation of cerebral blood flow in primates and NO synthase (NOS) immunoreactivity was demonstrated in the nerve plexus in the adventitia of the circle of Willis in primates. In a primate model of subarachnoid hemorrhage (SAH) adventitial NOS disappeared on day 7 after SAH, concurrently vasospasm, suggesting that NO loss plays a role in the pathogenesis of cerebral vasospasm after SAH. Thus, direct replacement of NO should reverse the vasospastic effect of any NO loss. In the primate model of vasospasm, intra-arterial infusions of NO solution and NO donor solution reversed arteriographic cerebral vasospasm, significantly increased cerebral blood flow, and decreased cerebral blood flow velocity. These findings further support a central role of NO in the pathogenesis of cerebral vasospasm and suggest the potential of a regional NO therapy for cerebral vasospasm. We also have explored the effects of the putative agents of vasospasm, oxyhemoglobin and its breakdown product methemoglobin in cell culture. These examine the possibility that vasospastic agents, such as, endothelin, may be released from tissues exposed to oxyhemoglobin and methemoglobin. While exposure to hemoglobin does not directly increase endothelin levels, hypoxia, a condition associated with a decrease in cerebral blood flow, causes dramatic increases in endothelin. Thus, endothelin may be responsible for secondary ischemia-producing effects associated with vasospasm after SAH. The most common type of cranial dural arteriovenous fistulas was shown to be treated effectively by simple interruption of the intrathecal venous drainage, a much simpler and safer procedure than the prior management of these patients.The lasting efficacy of a simple surgical procedure for patients with spinal dural arteriovenous fistulas, interruption of the vein draining the fistula intradurally, was demonstrated. A new type of tumor associated with von Hippel-Lindau (VHL) syndrome, low grade adenocarcinoma of the endolymphatic sac, was identified and shown to occur in at least 19% of VHL patients.
