Plasma endothelin and big endothelin concentrations and serum endothelin-converting enzyme activity following aneurysmal subarachnoid hemorrhage.
OBJECTIVE
Pathogenesis of delayed ischemia after aneurysmal subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET)-1 with its powerful and long-lasting vasoconstricting activity. In this prospective study the author investigated the correlations between serial plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 molar concentration ratio and serum endothelin-converting enzyme (ECE)-1 activity, and ischemic complications after SAH.


METHODS
To measure plasma ET-1 (51 patients), big ET-1 immunoreactivity (22 patients), and serum ECE-1 activity (13 patients), blood samples were obtained on admission, in the morning after aneurysm surgery, and during the 2nd week after hemorrhage in 51 consecutive patients (28 men and 23 women, with a mean age of 50.8 years) with aneurysmal SAH. Mean plasma concentrations of ET-1 in patients with SAH (mean +/- standard deviation: on admission, 4.2 +/- 2 pg/ml; after surgery, 4.3 +/- 2.2 pg/ml; and during the 2nd week after SAH, 3.7 +/- 1.9 pg/ml) differed from those in healthy volunteers (2.9 +/- 1.2 pg/ml; p < 0.01). Plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 ratio did not change significantly with elapsed time following SAH; however, serum ECE-1 activity during the 2nd week after SAH was higher in patients with SAH than that in controls (162 +/- 43 compared with 121 +/- 56 pg/ml, respectively; p = 0.028). Plasma ET-1 concentrations (p < 0.05) and the ET-1/big ET-1 ratios (p = 0.063) were higher but plasma big ET-1 concentrations were lower (p < 0.05) in patients who experienced symptomatic delayed cerebral ischemia, compared with other patients with SAH. In addition, in cases in which follow-up computerized tomography scans or magnetic resonance images demonstrated permanent ischemic lesions attributable to vasospasm, patients had higher ET-1 concentrations than did other patients with SAH.


CONCLUSIONS
The plasma ET-1 concentration correlates with delayed cerebral ischemia after SAH, suggesting that an increased ET conversion rate in the endothelium predicts ischemic symptoms. Increased serum ECE-1 activity during the 2nd week may reflect the severity of endothelial injury to cerebral arteries.
Juvela
Seppo
S
Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland. seppo.juvela@helsinki.fi
D000328:Adult; D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology; D019332:Endothelin-1 / Q000097:blood*; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000097:blood*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008666:Metalloendopeptidases; D008875:Middle Aged; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000473:pathology / Q000601:surgery; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000097:blood / Q000473:pathology
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes