Bilirubin and the induction of intracranial arterial spasm.
Although a number of substances which participate in the physiological control of vascular caliber have been proposed to play a causative role in cerebral vasospasm, none of these has been shown to induce the profound, sustained degree of constriction or the vasculopathy that characterize this disorder. The present study was undertaken to determine whether bilirubin, a hemoglobin breakdown product with detergent-like activity, accrued in incubated blood or in intracranial hematoma and whether topical application of bilirubin altered the caliber or morphology of cerebral arteries. As a model of blood residing in the subarachnoid space, sterile vials of cat blood and of human blood were incubated in vitro at 37 degrees C. The concentration of bilirubin in the supernatant of cat blood increased from a value of 0.27 +/- 0.3 mg% (mean +/- standard error of the mean) on Day 0 to a value of 9.57 +/- 2.4 mg% on Day 10; the respective values for human blood were 0.53 +/- 0.02 mg% and 13.4 +/- 5.4 mg%. Samples of intracranial hematoma that had been surgically removed from three patients between 4 and 11 days after hemorrhage yielded bilirubin levels from 2.1 to 15.2 mg%. Application of a bilirubin suspension of 5, 10, or 20 mg% in buffered Ringer's solution to cat basilar artery in vivo led to progressive and sustained constriction; at 4 hours the mean decrease in the width of the blood column was 34% +/- 2.1%. Ultrastructural analysis of these vessels showed widespread pathological changes similar to those associated with cerebral vasospasm. Application of a 10-mg% bilirubin suspension to the basilar artery of two baboons produced similar alterations. Minimal changes in diameter or morphology were observed in cat arteries bathed in buffer solution alone. These findings in animal models indicate that bilirubin may play a central role in the development of cerebral vasospasm.
Division of Neurological Surgery, University of Wisconsin, Madison.
T A
TA
Duff
J A
JA
Feilbach
Q
Q
Yusuf
G
G
Scott
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001488:Basilar Artery / Q000187:drug effects / Q000648:ultrastructure; D001663:Bilirubin / Q000097:blood* / Q000494:pharmacology; D002415:Cats; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000097:blood*; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D010215:Papio; D013997:Time Factors; D014661:Vasoconstriction
D001663:Bilirubin