Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.
Weil Institute of Emergency and Critical Care Medicine, Richmond, Virginia.
Microcirculation. 2019 Aug;26(6):e12537. doi: 10.1111/micc.12537. Epub 2019 Mar 26.
We hypothesized that mild hypothermia may improve brain microcirculation by reducing cerebral microvascular endothelial cells apoptosis, and this effect may be maximized by moving up the initiation of mild hypothermia from after return of spontaneous circulation (ROSC) to the start of cardiopulmonary resuscitation (CPR).
A total of 35 rats were randomized into the intra-arrest hypothermia group (IAH), post-resuscitation hypothermia group (PRH), normothermia group (NT), or the sham control group. A craniotomy exposed the parietal cortex for visualization of microcirculation. Ventricular fibrillation was electrically induced and untreated for 8 minutes, followed by 8 minutes of precordial compression and mechanical ventilation. Hypothermia (33 ± 0.5°C) in the IAH and PRH group was induced and maintained for 6 hours at the beginning of CPR or after ROSC, respectively. At baseline, 1, 3, and 6 hours, hemodynamic parameters were measured and the pial microcirculations were visualized with a sidestream dark field imaging video microscope. Microvascular flow index and perfused microvessel density (PMD) were calculated. Rats were euthanized, and brain tissues were removed at 3 and 6 hours separately. Expression of Bax, Bcl-2, and Caspase 3 in brain microvascular endothelial cells was examined by Western blot.
Microvascular flow index and PMD were significantly reduced after cardiac arrest and resuscitation (all P < 0.05), and the former was largely preserved by hypothermia regardless when the hypothermia treatment was induced (P < 0.05). Bax and Caspase 3 increased and Bcl-2 decreased significantly after resuscitation, and hypothermia treatment reversed the trend partly (all P < 0.05). A moderate correlation was observed between MFI and those proteins (Bcl-2/BAX: 3 hours: r = 0.730, P = 0.002; 6 hours: r = 0.743, P = 0.002).
Mild hypothermia improves cerebral microcirculatory blood supply, partly by inhibiting endothelial cell apoptosis. Mild hypothermia induced simultaneously with CPR has shown no additional benefit in microcirculation or endothelial cell apoptosis.
我们假设轻度低温可能通过减少脑微血管内皮细胞凋亡来改善脑微循环，并且通过将轻度低温的起始时间从自主循环恢复（ROSC）提前到心肺复苏（CPR）开始，这种效果可能会最大化。
共有 35 只大鼠随机分为停搏期低温组（IAH）、复苏后低温组（PRH）、常温组（NT）或假手术对照组。开颅术暴露顶骨皮层以可视化微循环。电诱导心室颤动并未经处理 8 分钟，随后进行 8 分钟的胸外按压和机械通气。IAH 和 PRH 组在 CPR 开始时或 ROSC 后分别诱导并维持 6 小时的低温（33±0.5°C）。在基线、1 小时、3 小时和 6 小时测量血流动力学参数，并使用侧流暗场成像视频显微镜可视化软脑膜微循环。计算微血管血流指数和灌注微血管密度（PMD）。大鼠在 3 小时和 6 小时时分别处死并取出脑组织。用 Western blot 检测脑微血管内皮细胞中 Bax、Bcl-2 和 Caspase 3 的表达。
心脏骤停和复苏后，微血管血流指数和 PMD 明显降低（均 P<0.05），低温治疗无论何时开始（低温诱导），前者均得到了很大的保留（P<0.05）。复苏后 Bax 和 Caspase 3 明显增加，Bcl-2 明显减少，低温治疗部分逆转了这种趋势（均 P<0.05）。MFI 与这些蛋白之间存在中度相关性（Bcl-2/BAX：3 小时：r=0.730，P=0.002；6 小时：r=0.743，P=0.002）。
轻度低温可改善脑微循环的血液供应，部分通过抑制内皮细胞凋亡。CPR 同时诱导的轻度低温对微循环或内皮细胞凋亡没有额外益处。
