Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.

Background and Purpose-Subarachnoid hemorrhage (SAH) causes acute vasoconstriction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide (NO) may contribute to acute vasoconstriction. Therefore we examined the effect of the NO donor N-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH. Methods-SAH was induced by the endovascular suture method in anesthetized rats. GSNO (1 mol/L/kg, nϭ31) or saline (nϭ21) was injected 5 minutes after SAH. Sham-operated rats received GSNO (1 mol/L/kg, nϭ5) 5 minutes after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH. SAH size was determined, and vascular measurements were made histologically. Results-GSNO had no effect on resting blood pressure, intracranial pressure, cerebral perfusion pressure, or CBF in sham-operated animals. However, administration of GSNO after SAH was associated with significantly increased CBF (161.6Ϯ26.6% versus saline 37. Key Words: cerebral blood flow Ⅲ glutamates Ⅲ nitric oxide Ⅲ subarachnoid hemorrhage Ⅲ vasoconstriction C erebral arteries respond to subarachnoid hemorrhage (SAH) with a biphasic contraction that begins minutes after the bleed and delayed vasospasm more than 48 hours later. 1-3 Although a great deal is known about the mechanisms and management of delayed vasospasm, less is known about the physiology, treatment, and importance of acute vasoconstriction. Different mechanisms may underlie the 2 processes, 4 and a great variety have been implicated. [5][6][7][8][9][10][11] Recently we have shown that acute vasoconstriction is associated with decreased cerebral blood flow (CBF), ischemic glutamate release, and premature mortality after experimental SAH. 12 If acute vasoconstriction could be pharmacologically attenuated, then SAH-induced brain injury could potentially be reduced.Resting cerebrovascular tone is maintained by a balance between opposing vasoconstrictive and vasodilatory forces, and both are pathologically altered in the acute phases of SAH. One of the most important of these is the resting vasodilatory influence of nitric oxide (NO). NO has been shown to induce endothelium-dependent vasodilatation via a cGMP-mediated See Editorial Comment, page 1961 mechanism. 13 Loss of endothelium-mediated vasodilatation 14,15 and decreased cGMP production 16,17 have been shown to contribute to vasospasm after SAH.Because administration of an NO donor after SAH should potentially restore c-GMP-dependent vasodilatation, a number of different NO donors have been tested for their ability to attenuate delayed vasospasm. 18 -21 Recent studies have suggested that sodium nitroprusside administered intrathecally 22 or intra-arterially 23 increases CBF acutely after SAH. In preliminary studies we have found that it also causes profound hypotension in this setting (J.B. Bederson, MD, et al, ...