Artikel
Activation of cerebral Endothelin-system after subarachnoid hemorrhage is reflected by the C-terminal fragment in cerebrospinal fluid
Die Aktivierung des zerebralen Endothelin-Systems nach Subarachnoidalblutung ist durch Messung des C-terminalen Fragmentes im Liquor nachvollziehbar
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Enhanced synthesis of Endothelin (ET)-1 is considered a key factor in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Stimulation of the activity of the cerebral ET-system has previously been concluded from an increased ET-1 content in cerebrospinal fluid (CSF) of patients suffering from SAH. However, these measurements did not reveal vasoacitve concentrations. In the present investigation we compared the concentrations of ET-1 and its vasoinactive companion peptide C-terminal fragment (CTF) to evaluate its prognostic value on the development of CVS.
Methods
Samples of CSF and plasma were obtained from 5 patients suffering from SAH (Hunt and Hess °IV) and developing delayed CVS as proven by angiography. The concentrations of ET-1 and CTF were analyzed by radioimmuno assay (RIA) in samples covering up to day 7 after bleeding.
Results
Plasma concentration of CTF was 3.5±0.8 (mean±SEM)-fold higher than ET-1 but without a correlation with the development of CVS. In contrast, ET-1 and CTF concentrations in CSF steadily increased after SAH. This increase was markedly more pronounced for CTF than for ET-1. Accordingly, the difference of the basal level to the maximum value was 83 ± 39 pg/ml for ET-1 and 154 ± 49 pg/ml for CTF. A significantly higher concentration of CTF versus ET-1 in CSF occurred from 3 day on. An increase of CTF concentration apparently preceded development of vasospasm.
Conclusions
Given an equimolar generation of ET-1 and CTF, concentration of CTF in CSF appears to reflect activation of the cerebral ET-system more precisely than ET-1. Maximum CSF concentrations of CTF are clearly in the range in which ET-1 exerts vasoconstriction. Thus, the present study suggests that the CTF level in CSF as a prognostic factor for development of CVS is superior compared to ET-1.