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Hypothermia revisited: Impact of ischaemic duration and between experiment variability

Rewell, SSJ, Jeffreys, AL, Sastra, SA, Cox, SF, Fernandez, JA, Aleksoska, E, van der Worp, HB, Churilov, L, Macleod, MR and Howells, DW ORCID: 0000-0002-2512-7724 2017 , 'Hypothermia revisited: Impact of ischaemic duration and between experiment variability' , Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 10 , pp. 3380-3390 , doi:

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To assess the true effect of novel therapies for ischaemic stroke, a positive control that can validate the experimental model and design is vital. Hypothermia may be a good candidate for such a positive control, given the convincing body of evidence from animal models of ischaemic stroke. Taking conditions under which substantial efficacy had been seen in a meta-analysis of hypothermia for focal ischaemia in animal models, we undertook three randomised and blinded studies examining the effect of hypothermia induced immediately following the onset of middle cerebral artery occlusion on infarct volume in rats (n = 15, 23, 264). Hypothermia to a depth of 33℃ and maintained for 130 min significantly reduced infarct volume compared to normothermia treatment (by 27–63%) and depended on ischaemic duration (F(3,244) = 21.242, p < 0.05). However, the protective effect varied across experiments with differences in both the size of the infarct observed in normothermic controls and the time to reach target temperature. Our results highlight the need for sample size and power calculations to take into account variations between individual experiments requiring induction of focal ischaemia.

Item Type: Article
Authors/Creators:Rewell, SSJ and Jeffreys, AL and Sastra, SA and Cox, SF and Fernandez, JA and Aleksoska, E and van der Worp, HB and Churilov, L and Macleod, MR and Howells, DW
Keywords: ischaemic stroke, animal models, hypothermia, positive control, ischaemic duration
Journal or Publication Title: Journal of Cerebral Blood Flow and Metabolism
Publisher: SAGE Publications
ISSN: 0271-678X
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Copyright Author(s) 2017

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