Univ Paris Est Créteil, INSERM, IMRB Créteil France.
Ecole Nationale Vétérinaire d'Alfort, IMRB, AfterROSC Network Maisons-Alfort France.
J Am Heart Assoc. 2024 Aug 20;13(16):e035617. doi: 10.1161/JAHA.124.035617. Epub 2024 Aug 19.
Brain injury is one of the most serious complications after cardiac arrest (CA). To prevent this phenomenon, rapid cooling with total liquid ventilation (TLV) has been proposed in small animal models of CA (rabbits and piglets). Here, we aimed to determine whether hypothermic TLV can also offer neuroprotection and mitigate cerebral inflammatory response in large animals.
Anesthetized pigs were subjected to 14 minutes of ventricular fibrillation followed by cardiopulmonary resuscitation. After return of spontaneous circulation, animals were randomly subjected to normothermia (control group, n=8) or ultrafast cooling with TLV (TLV group, n=8). In the latter group, TLV was initiated within a window of 15 minutes after return of spontaneous circulation and allowed to reduce tympanic, esophageal, and bladder temperature to the 32 to 34 °C range within 30 minutes. After 45 minutes of TLV, gas ventilation was resumed, and hypothermia was maintained externally until 3 hours after CA, before rewarming using heat pads (0.5 °C-1 °C/h). After an additional period of progressive rewarming for 3 hours, animals were euthanized for brain withdrawal and histological analysis. At the end of the follow-up (ie, 6 hours after CA), histology showed reduced brain injury as witnessed by the reduced number of Fluroro-Jade C-positive cerebral degenerating neurons in TLV versus control. IL (interleukin)-1ra and IL-8 levels were also significantly reduced in the cerebrospinal fluid in TLV versus control along with cerebral infiltration by CD3+ cells. Conversely, circulating levels of cytokines were not different among groups, suggesting a discrepancy between local and systemic inflammatory levels.
Ultrafast cooling with TLV mitigates neuroinflammation and attenuates acute brain lesions in the early phase following resuscitation in large animals subjected to CA.
脑损伤是心脏骤停 (CA) 后最严重的并发症之一。为了预防这种现象，在 CA 的小动物模型中提出了用全液体通气 (TLV) 进行快速冷却。在这里，我们旨在确定低温 TLV 是否也能为大型动物提供神经保护并减轻大脑炎症反应。
麻醉猪经历 14 分钟的心室颤动，随后进行心肺复苏。自主循环恢复后，动物随机接受常温（对照组，n=8）或 TLV 超速降温（TLV 组，n=8）。在后一组中，TLV 在自主循环恢复后 15 分钟的窗口期内开始，并允许在 30 分钟内将鼓膜、食管和膀胱温度降至 32 至 34°C 范围。TLV 30 分钟后，开始进行气体通气，并通过外部加热垫将体温维持在低温直至 CA 后 3 小时，然后开始复温（0.5°C-1°C/h）。在 CA 后 3 小时的进一步复温期间，动物被处死取脑并进行组织学分析。在随访结束时（即 CA 后 6 小时），组织学显示 TLV 组大脑损伤减少，Fluroro-Jade C 阳性大脑退行性神经元数量减少。TLV 组脑脊液中白细胞介素（IL）-1ra 和 IL-8 水平也明显低于对照组，且大脑内有 CD3+细胞浸润。相反，各组间循环细胞因子水平无差异，提示局部和全身炎症水平存在差异。
在 CA 后复苏的大型动物中，TLV 超速降温可减轻神经炎症，减轻早期急性脑损伤。
