Lamb Jessica A, Rajput Padmesh S, Lyden Patrick D
Department of Neurology, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Los Angeles, CA 90048, United States.
Department of Neurology, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Los Angeles, CA 90048, United States.
J Neurosci Methods. 2016 Jul 15;267:55-61. doi: 10.1016/j.jneumeth.2016.04.011. Epub 2016 Apr 21.
Hypothermia is the most potent protective therapy available for cerebral ischemia. In experimental models, cooling the brain even a single degree Celsius alters outcome after global and focal ischemia. Difficulties translating therapeutic hypothermia to patients with stroke or after cardiac arrest include: uncertainty as to the optimal treatment duration; best target-depth temperature; and longest time delay after which therapeutic hypothermia won't benefit. Recent results from human clinical trials suggest that cooling with surface methods provides insufficient cooling speed or control over target temperature.
Available animal models incorporate surface cooling methods that are slow, and do not allow for precise control of the target temperature.
To address this need, we developed a rapid, simple, inexpensive model for inducing hypothermia using a perivascular implanted closed-loop cooling circuit. The method allows precise control of the target temperature.
Using this method, target temperature for therapeutic hypothermia was reached within 13±1.07min (Mean±SE). Once at target, the temperature was maintained within 0.09°C for 4h.
This method will allow future experiments to determine under what conditions therapeutic hypothermia is effective, determine the optimal relationship among delay, duration, and depth, and provide the research community with a new model for conducting further research into mechanistic questions underlying the efficacy of therapeutic hypothermia.
低温是目前可用于脑缺血的最有效的保护性治疗方法。在实验模型中，即使将大脑温度降低1摄氏度也会改变全脑缺血和局灶性缺血后的结果。将治疗性低温应用于中风患者或心脏骤停患者时面临的困难包括：最佳治疗持续时间不确定；最佳目标深度温度不确定；以及治疗性低温不再有益的最长时间延迟不确定。人类临床试验的最新结果表明，采用体表降温方法时，降温速度不足或对目标温度的控制不足。
现有的动物模型采用的体表降温方法速度缓慢，且无法精确控制目标温度。
为满足这一需求，我们开发了一种快速、简单、廉价的模型，通过植入血管周围的闭环冷却回路来诱导低温。该方法可精确控制目标温度。
使用该方法，治疗性低温的目标温度在13±1.07分钟（平均值±标准误）内达到。一旦达到目标温度，温度可在4小时内维持在0.09°C以内。
该方法将使未来的实验能够确定治疗性低温在何种条件下有效，确定延迟、持续时间和深度之间的最佳关系，并为研究界提供一个新的模型，以进一步研究治疗性低温疗效背后的机制问题。
