Determining Candidate Hypobaric Hypoxia Profiles for Humane Killing of Laboratory Mice.

Determining Candidate Hypobaric Hypoxia Profiles for Humane Killing of Laboratory Mice.
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DOI:
10.3389/fvets.2022.834478
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发表时间:
2022
影响因子:
3.2
通讯作者:
Martin JE
Martin JE
中科院分区:
农林科学2区
文献类型:
--
作者:
Clarkson JM;McKeegan DEF;Sparrey J;Marchesi F;Leach MC;Martin JE

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每年有数百万只老鼠被用于科学研究,必须被人道地杀死。尽管存在重大的福利问题,但二氧化碳暴露仍然是最常见的杀戮方法,主要是因为没有实用且人道的替代方案。我们探讨了通过逐渐减压的低压缺氧是否会导致麻醉的雄性 C57BL/6 和 Balb/c 实验室小鼠进入不可恢复状态。我们的目的是确定这是否可以在可行的时间范围内以最小的病理后果实现,作为原理验证的步骤。在析因设计中对两种减压速率(75、150 ms−1)和三种轮廓形状(加速、线性、渐进)的系统评估表明,无论减压速率和形状如何,低压缺氧都能有效诱导麻醉实验小鼠的非恢复状态。在 75 ms−1 减压速率下,小鼠需要更长的时间才能达到非恢复状态(75 ms−1: 257 ± 8.96 与 150 ms−1: 214 ± 7.26 s),渐变和线性形状轮廓的延迟更长。加速成形的轮廓最不容易通过速率进行有意义的细化。唯一值得关注的病理变化是中耳充血和出血。这些发现表明低压缺氧具有潜力,后续工作将评估意识清醒的小鼠逐渐减压的福利后果,以确定最大程度减少与耳气压伤相关的福利危害的减压曲线。
Millions of mice are used annually in scientific research and must be humanely killed. Despite significant welfare concerns, carbon dioxide exposure remains the most common killing method, primarily because there is no practical and humane alternative. We explored whether hypobaric hypoxia via gradual decompression could induce a non-recovery state in anesthetized male C57BL/6 and Balb/c laboratory mice. We aimed to determine if this was possible in a feasible timescale with minimal pathological consequences, as a proof-of-principle step. Systematic evaluation of two decompression rates (75, 150 ms−1) and three profile shapes (accelerated, linear, gradual) in a factorial design revealed that hypobaric hypoxia effectively induced a non-recovery state in anesthetized laboratory mice, irrespective of decompression rate and shape. Mice took longer to reach a non-recovery state with the 75 ms−1 decompression rate (75 ms−1: 257 ± 8.96 vs. 150 ms−1: 214 ± 7.26 s), with longer latencies in gradual and linear shaped profiles. Accelerated shaped profiles were least susceptible to meaningful refinement via rate. The only pathological changes of concern were moderate middle ear congestion and hemorrhage. These findings suggest that hypobaric hypoxia has potential, and subsequent work will evaluate the welfare consequences of gradual decompression in conscious mice, to identify decompression profiles that minimize welfare harms associated with ear barotrauma.
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