Anesthetic and hemodynamic effects of the stereoisomers of medetomidine, an alpha 2-adrenergic agonist, in halothane-anesthetized dogs

Abstract

The anesthetic-sparing and hemodynamic effects of the stereoisomers of the highly selective alpha 2-adrenergic agonist medetomidine were studied in halothane-anesthetized dogs. Male beagles were anesthetized with halothane in oxygen. After a 2-hour equilibration period, halothane MAC and baseline hemodynamic functions were determined. DL-(n = 7), D- (n = 5), or L-medetomidine (n = 5) at 1, 3, and 10 micrograms/kg was administered via a right atrial port over 15 minutes while each dog was given halothane at the MAC dose for that animal. Twenty minutes after the end of infusion (when the hemodynamic variables were stable), hemodynamic function was reassessed. Halothane MAC was then redetermined. MAC for halothane significantly decreased after DL-medetomidine administration in a dose-dependent fashion to the extent that at the highest dose (10 micrograms/kg) the halothane MAC was less than 0.1%. This effect could be mimicked by the D-isomer, whereas the L-isomer was without effect. Neither isomer changed the mean arterial pressure, whereas only the D-isomer significantly decreased heart rate and cardiac output. Medetomidine, the highly selective alpha 2-adrenergic agonist, reduces the MAC for volatile anesthesia by a greater degree than with any other physiologic, pharmacologic, or pathologic intervention thus far reported. The fact that this effect is stereospecific suggests a structure activity relation that can be accounted for by a homogeneous receptor population. The role of medetomidine as a supplemental anesthetic agent appears promising and requires further investigation.