title: Temporal relationship between endothelin-1 concentrations and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  Endothelin 1 (ET-1) is a potent vasoconstrictor that may play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). However, data regarding its pathogenic role in the development of vasospasm are controversial. We planned a prospective, observational clinical study to investigate the temporal relationship between increased ET-1 production and cerebral vasospasm or other neurological sequelae after SAH.
  
  
  METHODS
  ET-1 levels in cerebrospinal fluid (CSF) were measured in 20 SAH patients from admission (within 24 hours from the bleeding) until day 7. Patients received a daily transcranial Doppler study and a neurological evaluation. On day 7, angiography was performed to verify the degree and extent of vasospasm. Patients were then classified as having (1) clinical vasospasm, (2) angiographic vasospasm, (3) no vasospasm, or (4) poor neurological condition without significant vasospasm (low Glasgow Coma Scale score [GCS]).
  
  
  RESULTS
  On admission, ET-1 levels were increased in the low-GCS group compared with the other groups (P=0.04). On day 4 ET-1 levels were not significantly different among groups, whereas on day 7 ET-1 levels were significantly increased in both the clinical vasospasm and low-GCS groups compared with the angiographic vasospasm and no vasospasm groups (P<0.005). Moreover, when the low-GCS group was excluded, there was a significant relationship between vasospasm grade and CSF ET-1 levels (R(2)=0.73).
  
  
  CONCLUSIONS
  CSF ET-1 levels were markedly elevated in patients with clinical manifestations of vasospasm (day 7) and with a poor neurological condition not related to vasospasm. However, ET-1 levels were low in clinical vasospasm patients before clinical symptoms were evident (day 4) and remained low in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe neuronal damage regardless whether this was due to vasospasm or to the primary hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurological deterioration but were not predictive of vasospasm.
authors.affiliation: Department of Anaesthesia, Toronto General Hospital, University of Toronto, Toronto, Canada. lmascia@teseo.it
authors.forename: L
authors.initials: L
authors.lastname: Mascia
authors.forename: L
authors.initials: L
authors.lastname: Fedorko
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: F
authors.initials: F
authors.lastname: Mohamed
authors.forename: K
authors.initials: K
authors.lastname: terBrugge
authors.forename: V M
authors.initials: VM
authors.lastname: Ranieri
authors.forename: M C
authors.initials: MC
authors.lastname: Wallace
mesh_terms: D002533:Cerebral Angiography; D018450:Disease Progression; D019332:Endothelin-1 / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000175:diagnosis; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000209:etiology*
chemical_list: D019332:Endothelin-1