Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan

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.

Can Endocrine Dysfunction Be Reliably Tested in Aged Horses That Are Experiencing Pain?

“…The administration of lidocaine in a continuous drip after surgical intervention cannot be conclusively assessed regarding the release of stress hormones, as it has a predominantly anti-inflammatory effect and, thus, contributes to the reduction of pain [ 42 , 43 ]. By contrast, the effects of α2 agonists on the concentrations of ACTH and cortisol are discussed contradictorily in the literature.…”

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

“…However, MK-467 should be employed with caution in dogs having the risk of hypoglycaemia owing to its insulin-releasing effect. Pakkanen et al (2018) conducted a study to explore whether or not the intravenous (IV) administration of romifidine or vatinoxan induce any variation in the plasma concentration of glucose or some metabolites and stress-related hormones in horses and also if vatinoxan can antagonise the possible adverse effects of romifidine when these agents are administered simultaneously. As per the study, the Plasma glucose concentration differed in all the three intravenous treatments: romifidine(80 μg/kg), vatinoxan (200 μg/kg) and the combination of both, with the glucose concentration to be highest following romifidine administration and the lowest following vatinoxan.…”

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl

“…Mitigation of peripheral cardiovascular effects have been described in many animal species [16][17][18] when administering vatinoxan together with various α 2 -agonists. Vatinoxan also alleviates the adverse metabolic effects of α 2 -agonists [19][20][21]. However, when administered intravenously (IV), it does not markedly affect sedation induced by α 2 -agonists [22,23].…”