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

IF 1.9 2区农林科学 Q2 VETERINARY SCIENCES

Veterinary anaesthesia and analgesia Pub Date : 2025-04-19 DOI:10.1016/j.vaa.2025.04.002

Emily Lindh , Anna Meller , Karoliina Alm , Piet Finckenberg , Marja Raekallio , Juhana Honkavaara

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引用次数: 0

Abstract

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.

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外周α 2-肾上腺素能拮抗剂伐替诺坦改善Wistar大鼠美托咪定-咪达唑仑镇静质量。

目的：观察外周α 2-肾上腺素受体拮抗剂伐替诺森对成年Wistar大鼠美托咪定-咪达唑仑镇静作用的影响。研究设计：随机、盲法、交叉研究（治疗间休息7天）。实验动物：雄性成年Wistar大鼠10只，体重311-332 g。方法：大鼠皮下注射美托咪定0.25 mg kg-1 +咪达唑仑2mg kg-1 （MM）、美托咪定0.125 mg kg-1 +咪达唑仑1mg kg-1（½MM）、MM +瓦替诺森5mg kg-1 （MMV）或½MM +瓦替诺森2.5 mg kg-1（½MMV） 4种皮下注射方法。通过测量翻正反射消失的时间来确定失去意识的时间。测量无创平均动脉血压（MAP）和脉搏率。结果：MMV[152(122-189)][中位值（范围）]明显短于MM[172(108-325)]或½MM[243(140-508)][中位值（范围）]（p = 0.050, p = 0.001）后的意识丧失时间（秒）。MMV术后BGC (mmol L-1)（9.6±1.8，平均±标准差）和½MMV（9.7±1.8）明显低于MM（18.1±4.1）或½MM(17.3±2.4)（均p < 0.001）。治疗后无死亡、低血压（MAP < 60 mmHg）或低血糖（BCG < 4.0）。结论及临床意义：通过减轻美托咪定在中枢神经系统外的相关作用，缩短意识丧失时间，瓦替诺森提高了SC美托咪定-咪达唑仑在实验大鼠中的镇静质量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Veterinary anaesthesia and analgesia 农林科学-兽医学

CiteScore

3.10

自引率

17.60%

发文量

审稿时长

97 days

期刊介绍： Veterinary Anaesthesia and Analgesia is the official journal of the Association of Veterinary Anaesthetists, the American College of Veterinary Anesthesia and Analgesia and the European College of Veterinary Anaesthesia and Analgesia. Its purpose is the publication of original, peer reviewed articles covering all branches of anaesthesia and the relief of pain in animals. Articles concerned with the following subjects related to anaesthesia and analgesia are also welcome: the basic sciences; pathophysiology of disease as it relates to anaesthetic management equipment intensive care chemical restraint of animals including laboratory animals, wildlife and exotic animals welfare issues associated with pain and distress education in veterinary anaesthesia and analgesia. Review articles, special articles, and historical notes will also be published, along with editorials, case reports in the form of letters to the editor, and book reviews. There is also an active correspondence section.