Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys
Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys
复制标题
选择性输注冷乳酸林格氏液引起的局部脑低温：恒河猴的可行性研究
DOI：
10.1080/01616412.2016.1187827
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发表时间：
2016-01-01
影响因子：
1.9
通讯作者：
Ji, Xunming
中科院分区：
文献类型：
--
作者：
Wang, Bincheng;Wu, Di;Ji, Xunming
背景和目的：亚低温作为一种治疗中风的神经保护策略已显示出良好的前景。由于全身降温有许多严重的副作用，限制了其临床应用。选择性脑降温，或局部脑低温，以前曾被提议作为一种替代治疗策略。本研究探讨局部输注冰冷乳酸林格液诱导恒河猴选择性脑低温的安全性、可行性和有效性。方法：实验选用雄性恒河猴8只。通过在大脑中动脉(MCA)近端置入微导管(n=4)，在大脑中动脉(MCA)供血区内注入100毫升冰镇(0°C)乳酸林格氏液，持续20分钟，以降低大脑中动脉(MCA)供血区的脑温。分别于输液前后监测生命体征、脑和直肠温度。应用经颅多普勒、磁共振成像(MRI)和数字减影血管造影术(DSA)评估脑血流量、脑血管反应性(CVR)、脑水肿和血管痉挛。另一组恒河猴(n=4)作为全身降温对照。结果：两组患者输液后血氧饱和度、血压、心率、血液学指标均在正常范围内。亚低温(<；35℃)在10min内(0.3℃/min)实现，局部皮质和纹状体局部灌注后维持20min。局部降温20min后纹状体内平均最低脑温为33.9±0.3℃。在通过全身输液冷却的动物中没有观察到这一点。局部输液直肠温度下降0.5±0.2℃，全身输液直肠温度下降0.5±0.3℃。根据MRI或基于DSA的灌流血管痉挛，选择性脑降温不会导致任何脑水肿。选择性脑低温对CVR无明显影响。结论：经微导管局部输注冰冷乳酸林格液是一种安全有效的选择性脑低温方法。这种降温方法有可能成为治疗急性缺血性卒中的新方法。
Background and Objective: Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer’s solution in rhesus monkeys. Methods: Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer’s solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls. Results: Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR. Conclusion: Local infusion of ice-cold lactated Ringer’s solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.