Temporal relationship between endothelin-1 concentrations and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

Background and Purpose-Endothelin 1 (ET-1) is a potent vasoconstrictor that may play a role in cerebral vasospasm following subarachnoid hemorrhage (S AH), However, data regarding its pathogenic role in the development of vaso spasm are controversial. We planned a prospective, observational clinical s tudy to investigate the temporal relationship between increased ET-I produc tion and cerebral vasospasm or other neurological sequelae after SAH. Methods-ET-1 levels in cerebrospinal fluid (CSF) were measured in 20 SAH pa tients from admission (within 24 hours from the bleeding) until day 7. Pati ents received a daily transcranial Doppler study and a neurological evaluat ion. 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 con dition without significant vasospasm (low Glasgow Coma Scale score [GCS]). Results-On admission, ET-1 levels were increased in the low-GCS group compa red with the other groups (P=0.04). On day 4 ET-1 levels were not significa ntly different among groups, whereas on day 7 ET-1 levels were significantl y increased in both the clinical vasospasm and low-GCS groups compared with the angiographic vasospasm and no vasospasm groups (P <0.005). Moreover, w hen the low-GCS group was excluded, there was a significant relationship be tween vasospasm grade and CSF ET-1 levels (R-2=0.73). Conclusions-CSF ET-1 levels were markedly elevated in patients with clinica l manifestations of vasospasm (day 7) and with a poor neurological conditio n not related to vasospasm. However, ET-1 levels were low in clinical vasos pasm patients before clinical symptoms were evident (day 4) and remained lo w in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe ne uronal damage regardless whether this was due to vasospasm or to the primar y hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurologic al deterioration but were not predictive of vasospasm.