Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest

Clinical trials of hypothermia after pediatric cardiac arrest have not seen robust improvement in functional outcome, possibly because of the long delay in achieving target temperature. Previous work in infant piglets showed that high nasal airflow, which induces evaporative cooling in the nasal mucosa, reduced regional brain temperature uniformly in half the time needed to reduce body temperature. The mouth is kept open to allow the high nasal airflow to easily exit. Here, we evaluated whether initiation of hypothermia with high transnasal airflow (32 L/min) provides neuroprotection without adverse effects in the setting of asphyxic cardiac arrest. Anesthetized, mechanically ventilated piglets (approximately 2-weeks-old) underwent sham-operated procedures (Group 1) or asphyxic cardiac arrest (Groups 2-6). The asphyxic insult consisted of reducing the inspired oxygen from 30% to 9.5-10% for 45 minutes (hypoxia period), then briefly increasing the inspired oxygen to 21% for 5 min (to imp..., Body temperature was measured with a rectal thermometer. Arterial pressure was measured with a pressure transducer connected to a fluid-filled catheter in the femoral artery. Heart rate was derived from the frequency of the arterial pressure pulses. Blood samples were periodically drawn from the femoral artery and analyzed for pH, PCO2, PO2, oxyhemoglobin saturation, and hemoglobin concentration on a Radiometer ABL800 Flex blood gas analyzer, with values corrected for body temperature. For histopathology, deeply anesthetized piglets underwent transcardial perfusion with cold phosphate-buffered saline, followed by ice-cold 4% paraformaldehyde. The brains were post-fixed overnight, then carefully removed from the skull. Each brain was bisected along the mid-sagittal plane and sectioned into a 20-mm coronal slab, ranging from -2 to +18 mm from the bregma. This process ensured the inclusion of key areas: the basal ganglia, sensorimotor cortex, and thalamus. The slab was further divided in..., , # Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest This study examined whether two techniques for inducing therapeutic hypothermia (standard body surface cooling and a novel technique in which high airflow through the nostrils to produce evaporative cooling of blood draining the nasal mucosa) after resuscitation from hypoxic-asphyxic cardiac arrest improves the survival of neurons in four brain regions (putamen, sensorimotor cortex, thalamus, and prefrontal cortex) in an infant swine model. For each cooling technique, separate groups were studied in which cooling commenced at either 10 or 120 minutes after resuscitation. The trial had 6 arms: Group 1 = Sham surgery and anesthesia Group 2 = Cardiac arrest + normothermia recovery Group 3 = Cardiac arrest + surface cooling from 10 minutes through 20 hours Group 4 = Cardiac arrest + transnasal cooling from 10 minutes through 120 minutes followed by surface c...针对小儿心脏骤停（pediatric cardiac arrest）后实施低温治疗的临床试验，尚未观察到功能预后（functional outcome）得到稳健改善，其潜在原因可能是达到目标体温的耗时过长。此前针对新生仔猪的研究表明，经鼻高流量气流可在鼻黏膜（nasal mucosa）诱导蒸发散热，能将脑局部降温的时长缩短至降低体温所需时长的一半。实验中需保持仔猪口腔张开，以使经鼻高流量气流能够顺利排出。本研究旨在评估，在窒息性心脏骤停（asphyxic cardiac arrest）模型中，采用经鼻高流量气流（32 L/min）启动低温治疗是否能在不产生不良反应的前提下发挥神经保护作用。 实验对象为经麻醉、机械通气的约2周龄仔猪，分别接受假手术操作（第1组）或窒息性心脏骤停造模（第2至6组）。窒息性损伤造模过程为：将吸入氧浓度从30%降至9.5%~10%，持续45分钟（缺氧期），随后短暂将吸入氧浓度提升至21%，持续5分钟以（原文截断）。 采用直肠温度计（rectal thermometer）测量体温。通过连接至股动脉（femoral artery）内置液导管的压力传感器（pressure transducer）测量动脉压。心率由动脉压脉冲频率计算得出。定期从股动脉采集血样，使用Radiometer ABL800 Flex型血气分析仪（blood gas analyzer）检测pH值、二氧化碳分压（PCO2）、氧分压（PO2）、氧合血红蛋白饱和度及血红蛋白浓度，检测结果已根据体温进行校正。 针对组织病理学（histopathology）检测，深度麻醉的仔猪需经心灌注（transcardial perfusion）冷磷酸盐缓冲液（phosphate-buffered saline, PBS），随后灌注冰浴冷却的4%多聚甲醛（paraformaldehyde）。脑组织经后固定过夜后，小心从颅腔中取出。每例脑组织沿矢状面中线切开，并切成距前囟（bregma）-2mm至+18mm的20mm厚冠状切片块。该取材方案可确保覆盖关键脑区：基底神经节（basal ganglia）、感觉运动皮层（sensorimotor cortex）及丘脑（thalamus）。该切片块将进一步被分割（原文截断）。 # 经鼻高流量常温气流诱导低温治疗在小儿心脏骤停模型中的神经保护作用 本研究以新生仔猪为模型，探讨缺氧窒息性心脏骤停复苏后，两种治疗性低温（therapeutic hypothermia）诱导方案——标准体表降温法，以及经鼻高流量气流对鼻黏膜引流血液进行蒸发散热的新型降温法——是否能改善4个脑区（壳核putamen、感觉运动皮层、丘脑及前额叶皮层prefrontal cortex）的神经元存活情况。针对每种降温方案，分别设置复苏后10分钟及120分钟开始降温的亚组。本实验共设6个实验组： 第1组：假手术+麻醉处理 第2组：心脏骤停+常温恢复 第3组：心脏骤停+自复苏后10分钟起持续20小时体表降温 第4组：心脏骤停+自复苏后10分钟起经鼻降温120分钟，随后辅以体表降温（原文截断）