Juguloarterial endothelin-1 gradients after severe traumatic brain injury.
BACKGROUND
Endothelin-1 (ET-1) is a potent vasoconstrictor and is thought to be responsible for secondary ischemia and vasogenic edema after traumatic brain injury (TBI). Both CSF and plasma concentrations have been shown to be increased after TBI, but there is little evidence to confirm an intracranial site of production.


METHODS
Using paired arterial and jugular venous bulb sampling, we measured arterial and jugular levels of ET-1 and its precursor, big endothelin (Big ET), and calculated juguloarterial (JA) gradients for the first 5 days post-TBI.


RESULTS
Arterial levels of both Big ET and ET-1 were maximal on day 1 post-TBI, and decreased thereafter (P < 0.05). Arterial levels of Big ET and ET-1 showed correlation across all 5 days of the study (r(2) = 0.25, P < 0.001). While there was no significant JA gradient for Big ET, significant gradients were observed for ET-1 on days 1-4 post-TBI (P < 0.05). There was no correlation between JA gradients for Big ET and ET-1 (r(2) < 0.1, P > 0.9). These data suggest parenchymal production of ET-1 by brain tissue with spill over into the blood, rather than local intraluminal cleavage of Big ET in the cerebral vasculature. Systemic ET-1 levels and JA gradients of ET-1 were unrelated to the injury severity, APACHE II score, Marshall Grade, the presence of subarachnoid or subdural hemorrhage, or eventual outcome.


CONCLUSIONS
These findings confirm the synthesis of Big ET and its cleavage to ET-1 within the brain after TBI. More work is needed to elucidate the pathophysiological role and the outcome impact of ET-1 generation after TBI.
Chatfield
Doris A
DA
Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Brahmbhatt
Darshan H
DH
Sharp
Tilly
T
Perkes
Iain E
IE
Outrim
Joanne G
JG
Menon
David K
DK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D002536:Cerebral Arteries; D003422:Critical Care; D018450:Disease Progression; D019332:Endothelin-1 / Q000097:blood* / Q000502:physiology; D005260:Female; D006801:Humans; D007601:Jugular Veins; D008297:Male; D008875:Middle Aged; D015599:Trauma Severity Indices; D055815:Young Adult
D019332:Endothelin-1