Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial.
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.



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.



In ToF children undergoing open heart surgery, RIPC attenuates myocardial IRI and improves the short-term prognosis.
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.
Qingping
Q
Wu
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.
Tingting
T
Wang
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.
Shiqiang
S
Chen
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.
Quanjun
Q
Zhou
State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong, China.|Department of Anaesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China.
Haobo
H
Li
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.
Na
N
Hu
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.
Yinglu
Y
Feng
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Nianguo
N
Dong
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.
Shanglong
S
Yao
State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong, China.|Department of Anaesthesiology, University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China.
Zhengyuan
Z
Xia
D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D011300:Preoperative Care / Q000379:methods*; D017216:Telemedicine / Q000379:methods*; D013771:Tetralogy of Fallot / Q000097:blood / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D019210:Troponin I