Wang Xueqing, Li Mo, Yang Zhengfei, Li Hongbin, Wang Yang, Tang Wanchun, Wu Yue, Xiao Peng, Jiang Shu, Shi Qindong, Lu Yihe, Li Hao
Department of Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Cardiovascular Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Shock. 2021 Sep 1;56(3):450-460. doi: 10.1097/SHK.0000000000001745.
Therapeutic temperature management (TTM) is the standard treatment protocol for unconscious post-resuscitation patients. However, there is still controversy about the ideal targeted temperature of mild hypothermia therapy. Additionally, studies about protective therapy for post-resuscitation intestinal injury are very limited. Therefore, this study was performed to explore: whether mild hypothermia therapy can exert a protective effect on post-resuscitation intestinal injury; the protective effect of different targeted temperatures on post-resuscitation intestinal injury and the ideal targeted temperature; the potential protective mechanism of mild hypothermia therapy for post-resuscitation intestinal injury.
Ventricular fibrillation was electrically induced and untreated for 6 min while defibrillation was attempted after 8 min of cardiopulmonary resuscitation in 15 rats. After successful resuscitation, animals were randomized into three groups: control; TTM-35; TTM-33. In animals of the control group, temperature was maintained at 37 ± 0.2°C for 6 h. In animals of the two TTM groups, temperature was maintained at 33 ± 0.2°C or 35 ± 0.2°C for 6 h, respectively. During mild hypothermia therapy, intestinal microcirculation was measured at 60, 240, and 360 min after resuscitation. Animals were euthanized 6.5 h after resuscitation. The morphological changes in the intestinal tissue, systemic and local inflammatory factors, and intestinal injury markers were measured and analyzed. The tight junction proteins in the intestinal epithelium, cell-cell contact protein E-cadherin expression, myosin light chain (MLC) and myosin light chain kinase levels, and the NF-κB p65 signaling pathway were analyzed by western blotting.
Compared with results in the control group, mild hypothermia therapy (TTM-33 and TTM-35 groups) significantly improved post-resuscitation intestinal microcirculation and pathological scores, decreased systemic and local intestinal tissue inflammatory factor levels, inhibited the NF-κB signaling pathway and downstream MLC phosphorylation, and significantly decreased MLC phosphorylation-associated loss of intestinal tight junction proteins and E-cadherin (P < 0.05). A 33°C target temperature could exert more protective effects than 35°C on post-resuscitation intestinal injury, such as improving intestinal microcirculation, decreasing intestinal ischemia factor iFABP, and plasma endotoxin levels, inhibiting the NF-κB signaling pathway and downstream MLC phosphorylation, and suppressing the loss of intestinal tight junctions and E-cadherin (P < 0.05).
Mild hypothermia therapy can improve post-resuscitation intestinal injury, and a targeted temperature of 33°C may confer more benefit for mitigation of intestinal injury as compared with a targeted temperature of 35°C.
治疗性体温管理（TTM）是复苏后昏迷患者的标准治疗方案。然而，关于轻度低温治疗的理想目标温度仍存在争议。此外，关于复苏后肠道损伤的保护性治疗的研究非常有限。因此，本研究旨在探讨：轻度低温治疗是否能对复苏后肠道损伤发挥保护作用；不同目标温度对复苏后肠道损伤的保护作用及理想目标温度；轻度低温治疗对复苏后肠道损伤的潜在保护机制。
对15只大鼠进行电诱导室颤并持续6分钟不治疗，在心肺复苏8分钟后尝试除颤。成功复苏后，将动物随机分为三组：对照组；TTM - 35组；TTM - 33组。对照组动物体温维持在37±0.2°C 6小时。两个TTM组动物体温分别维持在33±0.2°C或35±0.2°C 6小时。在轻度低温治疗期间，复苏后60、240和360分钟测量肠道微循环。复苏后6.5小时对动物实施安乐死。测量并分析肠道组织的形态学变化、全身和局部炎症因子以及肠道损伤标志物。通过蛋白质印迹法分析肠道上皮中的紧密连接蛋白、细胞间接触蛋白E - 钙黏蛋白表达、肌球蛋白轻链（MLC）和肌球蛋白轻链激酶水平以及NF - κB p65信号通路。
与对照组相比，轻度低温治疗（TTM - 33组和TTM - 35组）显著改善了复苏后肠道微循环和病理评分，降低了全身和局部肠道组织炎症因子水平，抑制了NF - κB信号通路及下游MLC磷酸化，并显著降低了与MLC磷酸化相关的肠道紧密连接蛋白和E - 钙黏蛋白的丢失（P < 0.05）。33°C的目标温度对复苏后肠道损伤的保护作用比35°C更强，如改善肠道微循环、降低肠道缺血因子iFABP和血浆内毒素水平，抑制NF - κB信号通路及下游MLC磷酸化，以及抑制肠道紧密连接和E - 钙黏蛋白的丢失（P < 0.05）。
轻度低温治疗可改善复苏后肠道损伤，与35°C的目标温度相比，33°C的目标温度可能对减轻肠道损伤更有益。
