Veterinary anaesthesia and analgesia · 2025
Peripheral alpha 2-adrenergic antagonist vatinoxan improves the quality of medetomidine-midazolam sedation in Wistar rats.
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Lindh Emily, Meller Anna, Alm Karoliina, Finckenberg Piet, Raekallio Marja, Honkavaara Juhana
Аннотация
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.
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.