The effect of tirilazad mesylate (U74006F) on cerebral oxygen consumption, and reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.
BACKGROUND
The 21-aminosteroids are a series of compounds designed to inhibit lipid peroxidation in the cell, and, as such, may have cerebral protective effects. The current study was performed to evaluate the effect of a 21-aminosteroid, tirilazad mesylate (U74006F), on cerebral blood flow, metabolism, and carbon dioxide reactivity.


METHODS
Using a double-blind study design, eight volunteers received tirilazad mesylate, and eight others received only vehicle. The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate (1.5 mg/kg) or vehicle. Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference. After both of the above cerebral blood flow measurements, arterial carbon dioxide tension was decreased by voluntary hyperventilation, and, later, increased by breathing an air/carbon dioxide mixture. The relative changes in cerebral blood flow induced by the PaCO2 variations were estimated from the changes in the arteriovenous oxygen content difference.


RESULTS
Blood pressure, pulse rate, and PaCO2 were similar before and after the infusion of tirilazad mesylate in both groups, and there was no difference between the groups. The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion. The slope of the regression line of relative change of estimated cerebral blood flow and PaCO2 (regression coefficients in both groups, > 0.90) was unchanged after infusion.


CONCLUSIONS
Tirilazad mesylate has no effect on cerebral blood flow, cerebral oxygen metabolism, or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.
Olsen
K S
KS
Department of Anesthesia, Rigshospitalet, University of Copenhagen, Denmark.
Videbaek
C
C
Agerlin
N
N
Krøll
M
M
Bøge-Rasmussen
T
T
Paulson
O B
OB
Gjerris
F
F
D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D016166:Free Radical Scavengers; D006801:Humans; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010313:Partial Pressure; D011281:Pregnatrienes / Q000494:pharmacology*; D011446:Prospective Studies
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D011281:Pregnatrienes; D002245:Carbon Dioxide; C053355:tirilazad