The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs.
Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.
Department of Equine and Small Animal Medicine, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. jussi.honkavaara@helsinki.fi
J M
JM
Honkavaara
F
F
Restitutti
M R
MR
Raekallio
E K
EK
Kuusela
O M
OM
Vainio
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis / Q000662:veterinary; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000494:pharmacology; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D058669:Adrenergic alpha-2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D011807:Quinolizines; C055732:vatinoxan; D020927:Dexmedetomidine