Reversal of cerebral vasospasm by the nitric oxide donor SNAP in an experimental model of subarachnoid haemorrhage

The constant release of nitric oxide (NO) is essential to maintain basal ce rebrovascular tone. Oxyhaemoglobin, liberated by lysis of red blood cells a fter subarachnoid haemorrhage binds NO and prevents its entry into vascular smooth muscle cells. While endothelium-dependent vasoconstriction is prese rved, decreased levels of NO inhibit endothelium-dependent relaxation and m ay cause vasospasm. S-nitrosothiols are potent vasodilators and precursors of NO. The authors' aim was to determine whether S-nitroso-N-acerylpenicill amine (SNAP). a stable S-nitrosothiol compound. could reverse vasospasm in an experimental vasospasm model in rabbit. Experimental subarachnoid haemor rhage (SAH) was induced in 37 New Zealand white rabbits. The animals were d ivided into four groups. Control (no SAH), SAH only, SAH plus saline and SA H plus SNAP. SNAP (15 mu g/kg/min) or 0.09% saline (equal volume) was infus ed 46 hours after induction of SAH. All animals were killed by perfusion fi xation 48 hours after SAH occurred. Basilar arteries were removed, sectione d and their cross sectional areas were evaluated in a blind manner, by ligh t microscopy and by using computer assisted morphometry. Experimental SAH e licited vasospasm in all animals of SAH only and SAH plus saline group. In animals treated with SNAP, arterial narrowing was markedly attenuated witho ut producing systemic hypotension. This widening achieved statistical signi ficance when compared to the arteries of the SAH only and SAH plus saline g roup (p < 0.01). This study indicates that the NO donor SNAP is a potential ly useful drug to reverse cerebral vasospasm due to SAH.