Rapid brain cooling method for acute cerebral ischemia・focal cerebral cooling by cold crystaloid intra-arterial perfusion in canine-

目的：脑低温是最有效的神经保护剂。然而，全身体温过低可能导致致命的并发症。假设在保持正常核心温度的情况下，选择性脑冷却可以实现局部低温神经保护，而不会产生全身低温的应激和副作用。因此，我们开发了一种新的方法，通过动脉灌注冷晶体溶液来实现脑温度的快速和选择性降低。方法：选用6只健康成年beagle犬，体重10.2-11.4kg，按照机构《实验动物护理使用指南》进行实验。冷却至4℃的林格氏液经4Fr导管动脉内灌注1.5 ~ 2.0 ml/min/kg。血液过滤系统排出过量水分。连续测量双侧脑组织温度、直肠温度、中心静脉温度、脑组织氧压、肺活量和心输出量。10周后处死几只狗并进行病理检查。结果：灌注后脑组织温度降至28℃（23.3±7.7min），可维持106±13.7min。对侧脑温、核温均降至34℃以下。通过血液过滤抽出等量的灌注液。全身动脉压、心率、心脏指数无波动。病理未见任何缺血性损伤。结论：动脉内冷晶体灌注治疗选择性脑低温在技术上是可行的，且靶温易于控制。低温诱导迅速，持续时间长，体温维持在正常范围内，无血流动力学不稳定。这种方法使我们能够有选择地、快速地、安全地冷却大脑的目标区域。该方法可用于急性脑损伤、缺血或难治性癫痫。少

Purpose: Cerebral hypothermia is the most potent neuroprotectant. Nevertheless, systemic hypothermia may result in fatal complication. It is hypothesized that selective cerebral cooling while maintaining normal core temperature would enable local hypothermic neuroprotection without the stress and side effects of systemic hypothermia. Thus, we have developed a novel method by which the rapid and selective reduction of brain temperature could achieve by intra-arterial perfusing cold crystalloid solution. Method: The experiments were performed on six adult healthy beagle dogs, weighting 10.2-11.4kg, and conducted in accordance with institutional Policies and Guidelines for Care and Use of Laboratory Animals. Ringer's solution cooled to 4 degree centigrade was infused by 1.5-2.0 ml/min/kg via 4Fr catheter intra-arterially. Excessive water was drawn out with hemo-filtration system. Bilateral brain tissue temperatures, rectal temperature, central venous temperature, brain tissue oxygen press … More ure and cardiac output were measured continuously. Several dogs were killed 10 weeks later and pathologically investigated. Results: The brain tissue temperature was fallen into 28 degree centigrade by perfusion for 23.3±7.7min and could be maintained for 106± 13.7min. The contra-lateral brain temperature, core temperature were cooled into less than 34 degree centigrade. The same quantity of perfusate was drawn out by hemo-filtration. The systemic arterial pressure, heart rate and cardiac index were not fluctuated. Pathological findings revealed not any ischemic damages pathologically. Conclusions: The data demonstrated that the intra-arterial cold crystalloid perfusion was technically feasible and useful for selective brain hypothermia, and target temperature are easily controlled. The induction of hypothermia was rapid and maintained for a long period of time, whereas the body temperature was maintained within the normal range and without hemodynamic instability. This method enables us to cool the objective region of the brain selectively, rapidly and safely. This method may useful for acute brain damages, ischemia or refractory epilepsy. Less