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，全身低温可能会导致致命的并发症。假设在维持正常核心体温的同时，选择性大脑降温将能够实现局部低温神经保护，而不会出现全身低温的压力和副作用。因此，我们开发了一种新的方法，通过动脉内灌流冷晶体溶液来实现快速和选择性的降温。方法：实验选用成年健康比格犬6只，体重10.2~11.4 kg，按照《实验动物保护和使用条例》的规定进行。林格液冷却至4℃，经4Fr导管动脉内注入1.5~2.0ml/min/kg。血液过滤系统排出过多的水。双侧脑组织温度、直肠温度、中心静脉温度、脑组织氧分压…连续监测更多尿量和心输出量。10周后，几只狗被杀，并进行了病理调查。结果：灌流23.3±7.7分钟，脑组织温度降至28℃，可维持106±13.7分钟。对侧脑温度、核心温度降温至34℃以下。血液滤过抽出等量的灌流液。全身动脉压、心率和心脏指数无波动。病理结果显示，病理上未见任何缺血性损害。结论：动脉冷晶体灌注用于选择性脑低温技术可行，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、快速和安全地冷却大脑的客观区域。这种方法可能对急性脑损伤、脑缺血或难治性癫痫有用。较少

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