Effects of the peripherally acting alpha(2)-adrenoceptor antagonist MK-467 on cardiopulmonary function in sheep sedated by intramuscular administration of medetomidine and ketamine and reversed by intramuscular administration of atipamezole

: Magdy Adam, Marja R. Raekallio, Kati M. Salla, Juhana M. Honkavaara, Sofia Männikkö, Mika Scheinin, Marena Kajula, Sari H. Mölsä, Outi M. Vainio

Publisher: AMER VETERINARY MEDICAL ASSOC

: 2018

: American Journal of Veterinary Research

: AM J VET RES

: 79

: 9

: 921

: 932

: 12

: 0002-9645

DOI: https://doi.org/10.2460/ajvr.79.9.921

: https://doi.org/10.2460/ajvr.79.9.921

OBJECTIVETo evaluate effects of the peripherally acting alpha(2)-adrenoceptor antagonist MK-467 on cardiopulmonary function in sheep sedated with medetomidine and ketamine.ANIMALS9 healthy adult female sheep.PROCEDURESEach animal received an IM injection of a combination of medetomidine (30 mu g/kg) and ketamine (I mg/kg; Med-Ket) alone and Med-Ket and 3 doses of MK 467 (150, 300, and 600 mu g/kg) in a randomized blinded 4-way cross-over study. Atipamezole (150 mu g/kg, IM) was administered 60 minutes later to reverse sedation. Cardiopulmonary variables and sedation scores were recorded, and drug concentrations in plasma were analyzed. Data were analyzed with a repeated-measures ANCOVA and 1-way ANOVA. Reference limits for the equivalence of sedation scores were set at 0.8 and 1.25.RESULTSHeart rate, cardiac output, and Pao(2) decreased and mean arterial blood pressure, central venous pressure, and systemic vascular resistance increased after Med-Ket alone. Administration of MK-467 significantly alleviated these effects, except for the decrease in cardiac output. After sedation was reversed with atipamezole, no significant differences were detected in cardiopulmonary variables among the treatments. Administration of MK467 did not significantly alter plasma concentrations of medetomidine, ketamine, norketamine, or atipamezole. Sedation as determined on the basis of overall sedation scores was similar among treatments.CONCLUSIONS AND CLINICAL RELEVANCEConcurrent administration of MK 467 alleviated cardiopulmonary effects in sheep sedated with Med-Ket without affecting sedation or reversal with atipamezole.