Peripheral alpha 2-adrenergic antagonist vatinoxan improves the quality of medetomidine-midazolam sedation in Wistar rats.

OBJECTIVE

To evaluate the effects of a peripheral alpha 2-adrenoceptor antagonist, vatinoxan, on medetomidine-midazolam sedation in adult Wistar rats.

STUDY

DESIGN

Randomized, blinded, crossover study (7 day rest period between treatments).

ANIMALS: A group of 10 male adult Wistar rats weighing 311-332 g.

METHODS

Rats were administered four subcutaneous (SC) treatments: medetomidine 0.25 mg kg-1 and midazolam 2 mg kg-1 (MM), medetomidine 0.125 mg kg-1 and midazolam 1 mg kg-1 (½MM), MM + vatinoxan 5 mg kg-1 (MMV) or ½MM + vatinoxan 2.5 mg kg-1 (½MMV). The time to loss of consciousness was determined by measuring the time to loss of the righting reflex. Noninvasive mean arterial blood pressure (MAP) and pulse rate were measured. After 55 minutes, blood glucose concentration (BGC) was analysed and atipamezole (1.25 mg kg-1 or 0.625 mg kg-1) and flumazenil (0.2 mg kg-1) were injected SC.

RESULTS

The time to loss of consciousness (seconds) was significantly shorter after MMV [152 (122-189)] [median (range)] than after MM [172 (108-325)] or ½MM [243 (140-508)] (p = 0.050, p = 0.001). BGC (mmol L-1) was significantly lower after MMV (9.6 ± 1.8, mean ± standard deviation) and ½MMV (9.7 ± 1.8) than after MM (18.1 ± 4.1) or ½MM (17.3 ± 2.4) (all p < 0.001). No mortality, hypotension (MAP < 60 mmHg) or hypoglycaemia (BCG < 4.0) were detected after any treatment.

CONCLUSIONS AND CLINICAL RELEVANCE: By mitigating the medetomidine-associated effects outside of the central nervous system and reducing the time to loss of consciousness, vatinoxan improved the quality of SC medetomidine-midazolam sedation in laboratory rats.