Rewell Sarah Sj, Jeffreys Amy L, Sastra Steven A, Cox Susan F, Fernandez John A, Aleksoska Elena, van der Worp H Bart, Churilov Leonid, Macleod Malcolm R, Howells David W
1 Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Heidelberg, Australia.
2 Department of Medicine, University of Melbourne, Melbourne, Australia.
J Cereb Blood Flow Metab. 2017 Oct;37(10):3380-3390. doi: 10.1177/0271678X16688704. Epub 2017 Jan 13.
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.
为评估新型缺血性中风疗法的真实效果，一个能够验证实验模型和设计的阳性对照至关重要。鉴于缺血性中风动物模型中有令人信服的证据，低温可能是这样一个阳性对照的良好候选者。根据对动物模型局灶性缺血低温治疗的荟萃分析中观察到显著疗效的条件，我们进行了三项随机双盲研究，考察大脑中动脉闭塞发作后立即诱导低温对大鼠梗死体积的影响（n = 15、23、264）。与正常体温治疗相比，将体温降至33℃并维持130分钟可显著减少梗死体积（减少27 - 63%），且这取决于缺血持续时间（F(3,244) = 21.242，p < 0.05）。然而，保护作用在不同实验中有所不同，正常体温对照组观察到的梗死大小以及达到目标温度的时间均存在差异。我们的结果强调，在进行样本量和效能计算时，需要考虑到个体实验之间因诱导局灶性缺血而产生的差异。
