title: Juguloarterial endothelin-1 gradients after severe traumatic brain injury.
abstract: 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.
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Doris A
authors.initials: DA
authors.lastname: Chatfield
authors.forename: Darshan H
authors.initials: DH
authors.lastname: Brahmbhatt
authors.forename: Tilly
authors.initials: T
authors.lastname: Sharp
authors.forename: Iain E
authors.initials: IE
authors.lastname: Perkes
authors.forename: Joanne G
authors.initials: JG
authors.lastname: Outrim
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
mesh_terms: 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
chemical_list: D019332:Endothelin-1