Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice-Assessing the degree of distress
Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice-Assessing the degree of distress
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DOI：
10.1371/journal.pone.0179588
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发表时间：
2017-06-15
期刊：
影响因子：
3.7
通讯作者：
Thoene-Reineke, Christa
中科院分区：
文献类型：
--
作者：
Hohlbaum, Katharina;Bert, Bettina;Thoene-Reineke, Christa
根据欧盟指令2010/63，手术的严重程度必须分为轻度、中度或重度。全身麻醉被认为是温和的，但指令没有区分单次麻醉和重复麻醉。因此，我们研究了重复给予异氟烷（最常用的吸入麻醉剂）对成年C57 BL/6 JRj小鼠健康的影响，与单次给药和未处理动物相比，每次给药6次，每次45分钟，间隔3-4天。对于麻醉的动物，监测兴奋、麻醉阶段和生命参数。使用行为测试组合评估麻醉后的健康状况，包括奢侈行为（如挖洞和筑巢行为）、小鼠鬼脸量表（MGS）、焦虑相关行为的自由探索范式、笼舍活动和活动的旋转棒测试以及摄食量和体重。此外，还测定了毛发皮质酮和粪便皮质酮代谢物。我们的研究结果表明，筑巢行为，家庭笼活动，体重和皮质酮浓度不受麻醉的影响，而在穴居行为，MGS，食物摄入量的变化，和自由探索的行为表明，幸福的小鼠受到影响的重复比单异氟烷麻醉。这种影响取决于动物的性别，雌性小鼠比雄性小鼠更容易受到影响。然而，重复异氟烷麻醉仅引起短期轻度痛苦和健康受损，主要发生在麻醉后即刻。最迟在末次麻醉后8天，健康状况稳定。因此，我们得出结论，当使用我们的麻醉方案时，C57 BL/6 JRj小鼠中单次和重复异氟烷麻醉的严重程度可归类为轻度。然而，在轻度严重程度类别中，重复异氟烷麻醉的等级高于单次异氟烷麻醉。此外，我们的研究结果表明，雄性和雌性小鼠可以不同地感知程序的严重性。
According to the EU Directive 2010/63, the severity of a procedure has to be classified as mild, moderate or severe. General anesthesia is thought to be mild, but the Directive does not differentiate between single and repeated anesthesia. Therefore, we investigated the impact of repeated administration of isoflurane, the most commonly used inhalation anesthetic, on the well-being of adult C57BL/6JRj mice, in comparison to single administrations and to untreated animals, when applied six times for 45 min at an interval of 3-4 days. For the animals anesthetized, excitations, phases of anesthesia, and vital parameters were monitored. Well-being after anesthesia was assessed using a behavioral test battery including luxury behavior like burrowing and nest building behavior, the Mouse Grimace Scale (MGS), the free exploratory paradigm for anxiety-related behavior, home cage activity and the rotarod test for activity, as well as food intake and body weight. Additionally, hair corticosterone and fecal corticosterone metabolites were measured. Our results show that nest building behavior, home cage activity, body weight, and corticosterone concentrations were not influenced by anesthesia, whereas changes in burrowing behavior, the MGS, food intake, and the free exploratory behavior indicated that the well-being of the mice was more affected by repeated than single isoflurane anesthesia. This effect depended on the sex of the animals, with female mice being more susceptible than male mice. However, repeated isoflurane anesthesia caused only short-term mild distress and impairment of well-being, mainly in the immediate postanesthetic period. Well-being stabilized at 8 days after the last anesthesia, at the latest. Therefore, we conclude that when using our anesthesia protocol, the severity of both single and repeated isoflurane anesthesia in C57BL/6JRj mice can be classified as mild. However, within the mild severity category, repeated isoflurane anesthesia ranks higher than single isoflurane anesthesia. Additionally, our results imply that male and female mice can differently perceive the severity of a procedure.