TY - JOUR

T1 - The effect of tirilazad mesylate (U74006F) on cerebral oxygen consumption, and reactivity of cerebral blood flow to carbon dioxide in healthy volunteers

AU - Olsen, K S

AU - Videbaek, C

AU - Agerlin, N

AU - Krøll, M

AU - Bøge-Rasmussen, T

AU - Paulson, O B

AU - Gjerris, Flemming

PY - 1993/10

Y1 - 1993/10

N2 - 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.

AB - 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.

KW - Adult

KW - Brain/blood supply

KW - Carbon Dioxide/blood

KW - Cerebrovascular Circulation/drug effects

KW - Double-Blind Method

KW - Free Radical Scavengers

KW - Humans

KW - Lipid Peroxides/antagonists & inhibitors

KW - Male

KW - Oxygen Consumption/drug effects

KW - Partial Pressure

KW - Pregnatrienes/pharmacology

KW - Prospective Studies

U2 - 10.1097/00000542-199310000-00006

DO - 10.1097/00000542-199310000-00006

M3 - Journal article

C2 - 8214745

VL - 79

SP - 666

EP - 671

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 4

ER -