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

Acta Vet Scand. 2018 May 9;60(1):27. doi: 10.1186/s13028-018-0380-x.

Abstract

Background: 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 (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.

Results: Plasma 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.

Conclusions: Romifidine 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.

Keywords: Glucose; Horse; Hyperglycaemia; Insulin; MK-467; Romifidine; Vatinoxan; α-2 adrenoceptor agonist.

MeSH terms

  • Administration, Intravenous / veterinary
  • Adrenergic alpha-2 Receptor Agonists / administration & dosage*
  • Adrenocorticotropic Hormone / blood*
  • Animals
  • Blood Glucose / metabolism*
  • Drug Combinations
  • Energy Metabolism / drug effects*
  • Female
  • Horses / metabolism*
  • Hydrocortisone / blood*
  • Imidazoles / administration & dosage
  • Insulin / blood*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Blood Glucose
  • Drug Combinations
  • Imidazoles
  • Insulin
  • romifidine
  • Adrenocorticotropic Hormone
  • Hydrocortisone