Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits.
BACKGROUND
The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH.


METHODS
CVS was induced using the one-haemorrhage rabbit model and confirmed by digital subtraction angiography of the rabbits' basilar artery on day 5. Prior to sacrifice, local CSF and basilar arterial plasma samples were obtained by a transclival approach to the basilar artery. Systemic arterial plasma samples were obtained. ET-1 levels were determined by immunometric technique (pg/ml +/- SEM) and total nitrate/nitrite level spectrophotometrically (micromol/l +/- SEM).


RESULTS
Angiographic CVS was documented after SAH induction (n = 12, P < 0.05). The ET-1 level in CSF was significantly elevated by 27.3% to 0.84 +/- 0.08 pg/ml in SAH animals (n = 7) in comparison to controls (0.66 +/- 0.04 pg/ml, n = 7, P < 0.05). There was no significant difference in ET-1 levels in systemic and basilar arterial plasma samples of SAH animals compared to controls. A significant lack of local NO metabolites was documented in basilar arterial plasma after SAH (36.8 +/- 3.1 micromol/l, n = 6) compared to controls (61.8 +/- 6.2 micromol/l, n = 6, P < 0.01).


CONCLUSIONS
This study demonstrates that an elevated ET-1 level in CSF and local lack of NO in the basilar arterial plasma samples are associated with CVS after experimental SAH.
Department of Neurosurgery, University Hospital Berne, Berne, Switzerland.
Volker
V
Neuschmelting
Serge
S
Marbacher
Ali-Reza
AR
Fathi
Stephan M
SM
Jakob
Javier
J
Fandino
D015901:Angiography, Digital Subtraction; D000818:Animals; D001488:Basilar Artery / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000097:blood* / Q000134:cerebrospinal fluid; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D015854:Up-Regulation / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000209:etiology* / Q000503:physiopathology
D019332:Endothelin-1; D009569:Nitric Oxide