Abstract
BackgroundRomifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. The aim of our study was to investigate the effects of intravenous romifidine and vatinoxan, alone and combined, on plasma concentrations of glucose and some stress-related hormones and metabolites in horses.ResultsPlasma glucose concentration differed between all intravenous treatments: romifidine (80 μg/kg; ROM), vatinoxan (200 μg/kg; V) and the combination of these (ROM + V). Glucose concentration was the highest after ROM and the lowest after V. Serum FFA concentration was higher after V than after ROM or ROM + V. The baseline serum concentration of insulin varied widely between the individual horses. No differences were detected in serum insulin, cortisol or plasma adrenocorticotropic hormone (ACTH) concentrations between the treatments. Plasma lactate, serum triglyceride or blood sodium and chloride concentrations did not differ from baseline or between the treatments. Compared with baseline, plasma glucose concentration increased after ROM and ROM + V, serum cortisol, FFA and base excess increased after all treatments and plasma ACTH concentration increased after V. Serum insulin concentration decreased after V and blood potassium decreased after all treatments.ConclusionsRomifidine induced hyperglycaemia, which vatinoxan partially prevented despite of the variations in baseline levels of serum insulin. The effects of romifidine and vatinoxan on the insulin concentration in horses need further investigation.
Highlights
Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine
The aim of this study was to explore whether the intravenous (IV) administration of romifidine or vatinoxan induces changes in plasma concentrations of glucose or some metabolites and stress-related hormones in horses, and whether vatinoxan is able to antagonise the possible effects of romifidine when these agents are administered simultaneously
These findings are in agreement with previous studies from horses treated with romifidine [1], detomidine [3, 18] and dogs treated with xylazine, medetomidine and dexmedetomidine [22, 30]
Summary
Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. Romifidine is an α-2 adrenoceptor agonist which is commonly used to induce sedation and analgesia in horses In addition to their sedative and analgesic effects, α-2 adrenoceptor agonists have a marked effect on plasma concentrations of glucose and some stress-related hormones and metabolites; romifidine, xylazine and detomidine increase plasma glucose concentrations by inhibiting insulin release from pancreatic β-cells in horses [1, 2], ponies [3] and mice [4]. In theory, decreased insulin concentration could result in hyperkalemia through diminished cellular K+ influx, as shown in dogs and humans [10]
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