The comparative hypoxaemic effect of four alpha(2) adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep

In the present study, the hypoxaemic potential of four alpha(2) agonists possessing different selectivity for alpha(2) adrenoceptors and of a saline placebo was studied in five clinically healthy sheep using a randomized Latin square design and equipotent sedative doses, Baseline values for heart rate (HR), mean arterial pressure (MAP), arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, respiration rate and maximum change in pleural pressure (Delta Ppl) were obtained, followed by the intravenous administration of either: xylazine (150 mu g/kg); romifidine (50 mu g/kg); detomidine (30 mu g/kg): medetomidine (10 mu g/kg) or placebo. Subsequent recordings were made up to 60 min after drug administration, No significant (P less than or equal to 0.05) alterations in any variable occurred with placebo, All the alpha(2) agonists significantly (P less than or equal to 0.05) decreased PaO2 Levels without a significant (P less than or equal to 0.05) change in PaCO2. The lowest PaO2 values were 29-42 mm Hg (3.9-5.5 kPa) with no significant difference between drugs. Respiratory rate and Delta Ppl increased significantly within 2 min of drug administration: the duration of this effect varied with the alpha(2) agonist, lasting longest with romifidine, As compared to the saline treated group, a significant increase in MAP was observed up to 10 min after administration of romifidine and detomidine, however, a significant decrease was seen at 10 and 45 min after xylazine and medetomidine, respectively, The alpha(2) agonists studied induced a similar change in PaO2 at peak effect, despite their reported variable selectivity for alpha(2) vs. alpha(1) adrenoceptors.