Objective

To compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine–ketamine–midazolam combination with or without vatinoxan (MK-467), a peripherally acting α₂-adrenoceptor antagonist.

Study design

Randomized, blinded, crossover study.

Animals

A group of nine healthy Patagonian maras (Dolichotis patagonum).

Methods

Maras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg^–1) + ketamine (5 mg kg^–1) + midazolam (0.1 mg kg^–1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg^–1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO₂, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05).

Results

Vatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols.

Conclusions and clinical relevance

In Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.

中文翻译：

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Vatinoxan 对巴塔哥尼亚沼泽（Dolichotis patagonum）中美托咪定-氯胺酮-咪达唑仑固定的影响

客观的

为了比较心血管和通气效果，固定化和质量上具有或不具有vatinoxan（MK-467）一个美托咪定，氯胺酮咪达唑仑组合的组织灌注的影响，外周作用α ₂ -肾上腺素受体拮抗剂。

学习规划

随机、盲法、交叉研究。

动物

一组九只健康的巴塔哥尼亚马拉斯 ( Dolichotis patagonum)。

方法

Maras 被固定两次：1) 盐酸美托咪定 (0.1 mg kg ^–1 ) + 氯胺酮 (5 mg kg ^–1 ) + 咪达唑仑 (0.1 mg kg ^–1 ) (MKM) + 盐水或 2) MKM + 盐酸伐替诺生 (0.8 mg) kg ^–1 )，肌肉注射。药物在同一个注射器中混合。注射后20、30、40分钟测量有创血压、心率、呼吸频率、呼气末CO ₂、血红蛋白氧饱和度、肌肉氧合，计算动静脉氧含量差值。评估肌肉张力、下巴张力、自发性眨眼和眼睑反射。记录初始效果、卧床、初始唤醒和头部控制的时间。配对t检验，Wilcoxon 配对符号秩检验和方差分析用于比较方案；( p < 0.05)。

结果

Vatinoxan在 20 和 40 分钟之间显着降低收缩压 ( p  = 0.0002)、平均 (MAP; p < 0.0001) 和舒张压 ( p < 0.0001)。使用 MKM 和 MKM + vatinoxan 的 30 分钟 MAP（平均值 ± 标准偏差）分别为 105 ± 12 和 71 ± 14 mmHg。没有vatinoxan，四只动物有高血压（MAP > 120 mmHg），而有vatinoxan，四只动物有低血压（MAP < 60 mmHg）。MKM 显着更频繁地出现肌肉和下巴张力（均p  = 0.039）。其他测量在协议之间没有显着差异。

结论和临床相关性

在巴塔哥尼亚 maras 中，vatinoxan 减弱了美托咪定引起的血压升高。MKM 更频繁地出现肌肉和下巴张力，表明使用 vatinoxan 固定的质量更深。