Determining candidate hypobaric hypoxia profiles for humane killing of laboratory mice

Clarkson, J. M. , McKeegan, D. E.F. , Sparrey, J., Marchesi, F. , Leach, M. C. and Martin, J. E. (2022) Determining candidate hypobaric hypoxia profiles for humane killing of laboratory mice. Frontiers in Veterinary Science, 9, 834478. (doi: 10.3389/fvets.2022.834478) (PMID:35400097) (PMCID:PMC8988232)

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Abstract

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.

Item Type:Articles
Additional Information:The authors would like to thank the Biotechnology and Biological Sciences Research Council (BBSRC) for funding the research project (BB/S007210/1). The Roslin Institute was funded by a BBSRC Institute Strategic Program Grant BB/P013759/1.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marchesi, Dr Francesco and McKeegan, Dr Dorothy and Clarkson, Dr Jasmine and Leach, Dr Matthew
Authors: Clarkson, J. M., McKeegan, D. E.F., Sparrey, J., Marchesi, F., Leach, M. C., and Martin, J. E.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Frontiers in Veterinary Science
Publisher:Frontiers Media
ISSN:2297-1769
ISSN (Online):2297-1769
Copyright Holders:Copyright © 2022 Clarkson, McKeegan, Sparrey, Marchesi, Leach and Martin
First Published:First published in Frontiers in Veterinary Science 9: 834478
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1250

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303692Decompression killing of laboratory rodents: a humane alternative to carbon dioxide?Dorothy McKeeganBiotechnology and Biological Sciences Research Council (BBSRC)BB/S007210/1Institute of Biodiversity, Animal Health and Comparative Medicine