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 cerebrovascular tone. Oxyhaemoglobin, liberated by lysis of red blood cells after subarachnoid haemorrhage binds NO and prevents its entry into vascular smooth muscle cells. While endothelium-dependent vasoconstriction is preserved, decreased levels of NO inhibit endothelium-dependent relaxation and may cause vasospasm. S-nitrosothiols are potent vasodilators and precursors of NO. The authors' aim was to determine whether S-nitroso-N-acetylpenicillamine (SNAP), a stable S-nitrosothiol compound, could reverse vasospasm in an experimental vasospasm model in rabbit. Experimental subarachnoid haemorrhage (SAH) was induced in 37 New Zealand white rabbits. The animals were divided into four groups. Control (no SAH), SAH only, SAH plus saline and SAH plus SNAP. SNAP (15 micrograms/kg/min) or 0.09% saline (equal volume) was infused 46 hours after induction of SAH. All animals were killed by perfusion fixation 48 hours after SAH occurred. Basilar arteries were removed, sectioned and their cross sectional areas were evaluated in a blind manner, by light microscopy and by using computer assisted morphometry. Experimental SAH elicited vasospasm in all animals of SAH only and SAH plus saline group. In animals treated with SNAP, arterial narrowing was markedly attenuated without producing systemic hypotension. This widening achieved statistical significance when compared to the arteries of the SAH only and SAH plus saline group (p < 0.01). This study indicates that the NO donor SNAP is a potentially useful drug to reverse cerebral vasospasm due to SAH.
Kiriş
T
T
Neurosurgery Department, Medical Faculty of Istanbul, University of Istanbul, Turkey.
Karasu
A
A
Yavuz
C
C
Erdem
T
T
Unal
F
F
Hepgül
K
K
Baloğlu
H
H
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000473:pathology / Q000503:physiopathology*
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D010396:Penicillamine