远程缺血预处理对法洛四联症根治术患儿的心脏保护作用：一项随机对照试验。
Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial.
机构信息
Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
出版信息
Eur Heart J. 2018 Mar 21;39(12):1028-1037. doi: 10.1093/eurheartj/ehx030.
AIMS
Remote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial IRI in children with tetralogy of Fallot (ToF), a severe cyanotic congenital cardiac disease, undergoing open heart surgery are unclear. We hypothesized that RIPC can confer cardioprotection in children undergoing ToF repair surgery.
METHODS AND RESULTS
Overall, 112 ToF children undergoing radical open cardiac surgery using cardiopulmonary bypass (CPB) were randomized to either a RIPC group (n = 55) or a control group (n = 57). The RIPC protocol consisted of three cycles of 5-min lower limb occlusion and 5-min reperfusion using a cuff-inflator. Serum inflammatory cytokines and cardiac injury markers were measured before surgery and after CPB. Right ventricle outflow tract (RVOT) tissues were collected during the surgery to assess hypoxia-inducible factor (Hif)-1α and other signalling proteins. Cardiac mitochondrial injury was assessed by electron microscopy. The primary results showed that the length of stay in the intensive care unit (ICU) was longer in the control group than in the RIPC group (52.30 ± 13.43 h vs. 47.55 ± 10.34 h, respectively, P = 0.039). Patients in the control group needed longer post-operative ventilation time compared to the RIPC group (35.02 ± 6.56 h vs. 31.96 ± 6.60 h, respectively, P = 0.016). The levels of post-operative serum troponin-T at 12 and 18 h, CK-MB at 24 h, as well as the serum h-FABP levels at 6 h, after CPB were significantly lower, which was coincident with significantly higher protein expression of cardiac Hif-1α, p-Akt, p-STAT3, p-STAT5, and p-eNOS and less vacuolization of mitochondria in the RIPC group compared to the control group.
CONCLUSION
In ToF children undergoing open heart surgery, RIPC attenuates myocardial IRI and improves the short-term prognosis.
目的
通过对远处组织进行短暂缺血来实现远程缺血预处理（RIPC），可以保护接受心脏直视手术的儿童免受心肌缺血再灌注损伤（IRI），但在合并症患者中的有效性存在争议。RIPC 在接受心脏直视手术的法洛四联症（ToF）儿童中的有效性和对心肌 IRI 的作用机制尚不清楚，ToF 是一种严重的发绀性先天性心脏病。我们假设 RIPC 可以为接受 ToF 修复手术的儿童提供心脏保护。
方法和结果
共有 112 名接受体外循环（CPB）下根治性心脏直视手术的 ToF 患儿被随机分为 RIPC 组（n=55）或对照组（n=57）。RIPC 方案包括三个循环的 5 分钟下肢闭塞和 5 分钟再灌注，使用充气袖带。在手术前和 CPB 后测量血清炎症细胞因子和心脏损伤标志物。在手术过程中收集右心室流出道（RVOT）组织，以评估缺氧诱导因子（Hif）-1α和其他信号蛋白。通过电子显微镜评估心脏线粒体损伤。主要结果显示，对照组患者在重症监护病房（ICU）的停留时间长于 RIPC 组（分别为 52.30±13.43 小时和 47.55±10.34 小时，P=0.039）。与 RIPC 组相比，对照组患者术后通气时间更长（分别为 35.02±6.56 小时和 31.96±6.60 小时，P=0.016）。CPB 后 12 小时和 18 小时的血清肌钙蛋白-T、24 小时的 CK-MB 以及 6 小时的血清 h-FABP 水平均较低，而 RIPC 组的心脏 Hif-1α、p-Akt、p-STAT3、p-STAT5 和 p-eNOS 蛋白表达较高，以及线粒体空泡化较少。
结论
在接受心脏直视手术的 ToF 儿童中，RIPC 可减轻心肌 IRI，并改善短期预后。
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