Omileke Daniel, Pepperall Debbie, Bothwell Steven W, Mackovski Nikolce, Azarpeykan Sara, Beard Daniel J, Coupland Kirsten, Patabendige Adjanie, Spratt Neil J
The School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
Hunter Medical Research Institute, New Lambton, NSW, Australia.
Front Neurol. 2021 Sep 20;12:684353. doi: 10.3389/fneur.2021.684353. eCollection 2021.
There is a transient increase in intracranial pressure (ICP) 18-24 h after ischaemic stroke in rats, which is prevented by short-duration hypothermia using rapid cooling methods. Clinical trials of long-duration hypothermia have been limited by feasibility and associated complications, which may be avoided by short-duration cooling. Animal studies have cooled faster than is achievable in patients. We aimed to determine whether gradual cooling at a rate of 2°C/h to 33°C or 1°C/h to 34.5°C, with a 30 min duration at target temperatures, prevented ICP elevation and reduced infarct volume in rats. Transient middle cerebral artery occlusion was performed, followed by gradual cooling to target temperature. Hypothermia to 33°C prevented significant ICP elevation (hypothermia ΔICP = 1.56 ± 2.26 mmHg vs normothermia ΔICP = 8.93 ± 4.82 mmHg; = 0.02) and reduced infarct volume (hypothermia = 46.4 ± 12.3 mm vs normothermia = 85.0 ± 17.5 mm; = 0.01). Hypothermia to 34.5°C did not significantly prevent ICP elevation or reduce infarct volume. We showed that gradual cooling to 33°C, at cooling rates achievable in patients, had the same ICP preventative effect as traditional rapid cooling methods. This suggests that this paradigm could be translated to prevent delayed ICP rise in stroke patients.
大鼠缺血性卒中后18 - 24小时颅内压(ICP)会出现短暂升高,采用快速冷却方法进行短时间低温治疗可预防这种情况。长时间低温治疗的临床试验受到可行性和相关并发症的限制,而短时间冷却可能避免这些问题。动物研究中的冷却速度比在患者中所能达到的速度更快。我们旨在确定以2°C/h的速度逐渐冷却至33°C或以1°C/h的速度逐渐冷却至34.5°C,并在目标温度下持续30分钟,是否能预防大鼠ICP升高并减少梗死体积。进行短暂大脑中动脉闭塞,随后逐渐冷却至目标温度。冷却至33°C可预防显著的ICP升高(低温时ΔICP = 1.56 ± 2.26 mmHg,常温时ΔICP = 8.93 ± 4.82 mmHg;P = 0.02)并减少梗死体积(低温时为46.4 ± 12.3 mm³,常温时为85.0 ± 17.5 mm³;P = 0.01)。冷却至34.5°C并未显著预防ICP升高或减少梗死体积。我们发现,以患者所能达到的冷却速度逐渐冷却至33°C,与传统快速冷却方法具有相同的预防ICP升高的效果。这表明这种模式可转化用于预防卒中患者延迟性ICP升高。