Zhou Wenwu, Zeng Debing, Chen Renwei, Liu Jian, Yang Guangxian, Liu Pingbo, Zhou Xinmin
Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha, Hunan, China.
Pediatr Cardiol. 2010 Jan;31(1):22-9. doi: 10.1007/s00246-009-9536-9. Epub 2009 Sep 29.
Open heart surgery supported by cardiopulmonary bypass is associated with heart and lung ischemia-reperfusion injury (IRI). Limb remote ischemic preconditioning (RIPC) reduces injury caused by ischemia-reperfusion in multiple distant organs. We conducted a prospective clinical trial (randomized and controlled) to test the feasibility and safety of limb RIPC, as well as its protective effects against myocardial and pulmonary IRI for infants undergoing repair of simple congenital heart defects. Infants undergoing repair of ventricular septal defects were enrolled in our study and randomly assigned to one of two treatment groups: limb RIPC or control. RIPC was induced twice (24 h and 1 h preoperatively) via three 5-min cycles of ischemia and reperfusion on the left upper arm using a blood pressure cuff. Lung compliance, respiratory index (RI), and cardiac inotropic score (IS) were calculated for each patient. Serum concentrations of the following factors were measured perioperatively: interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha; lactate dehydrogenase (LDH), creatine kinase (CK), and its isoenzyme (CK-MB), and troponin I (TnI); malondialdehyde (MDA) and superoxide dismutase (SOD). The expression of heat shock protein 70 (HSP 70) in cardiomyocytes was analyzed by Western blot. Surgical outcomes, including limb movement and sensory function, were recorded in detail. Sixty infants weighting less than 7 kg were studied, with 30 patients in the RIPC group and 30 in the control group. Within 6 months of discharge from the hospital, no limb disability, sensory disturbance, or other surgical complications were found in any patient. Compared with the control group, patients in the RIPC group had higher Cs and Cd, along with lower RI and IS at various postoperative phases. At the beginning of the operation, serum concentrations of IL-6, IL-8, IL-10, TNF-alpha, LDH, CK, and TnI were higher in the RIPC group than the control group. Postoperatively, release of cytokines and leakage of heart enzymes were attenuated in the RIPC group; serum concentrations of cytokines and heart enzymes were lower in the RIPC group at some, but not all, postoperative time points. Furthermore, the RIPC group had lower coronary sinus venous concentrations of MDA and higher concentrations of SOD. Similarly, the expression of HSP 70 was upregulated in cardiomyocytes from the RIPC group. Limb RIPC can be applied safely and easily in infants, can attenuate systemic inflammatory response syndrome, and can increase systemic tolerance to IRI, imparting a protective effect against myocardial and pulmonary IRI. The expression of HSP 70 has an important role in the mechanism of action for RIPC.
体外循环支持下的心脏直视手术与心肺缺血再灌注损伤（IRI）相关。肢体远程缺血预处理（RIPC）可减轻多个远处器官缺血再灌注所致的损伤。我们开展了一项前瞻性临床试验（随机对照），以测试肢体RIPC的可行性和安全性，以及其对接受简单先天性心脏病修复术的婴儿心肌和肺IRI的保护作用。接受室间隔缺损修复术的婴儿被纳入我们的研究，并随机分为两个治疗组之一：肢体RIPC组或对照组。使用血压袖带在上臂通过三个5分钟的缺血和再灌注周期诱导RIPC两次（术前24小时和1小时）。计算每位患者的肺顺应性、呼吸指数（RI）和心脏变力评分（IS）。围手术期测量以下因子的血清浓度：白细胞介素（IL）-6、IL-8、IL-10和肿瘤坏死因子（TNF）-α；乳酸脱氢酶（LDH）、肌酸激酶（CK）及其同工酶（CK-MB）和肌钙蛋白I（TnI）；丙二醛（MDA）和超氧化物歧化酶（SOD）。通过蛋白质印迹法分析心肌细胞中热休克蛋白70（HSP 70）的表达。详细记录手术结果，包括肢体运动和感觉功能。研究了60名体重小于7kg的婴儿，RIPC组和对照组各30例。出院后6个月内，未发现任何患者有肢体残疾、感觉障碍或其他手术并发症。与对照组相比，RIPC组患者在术后各阶段的Cs和Cd较高，而RI和IS较低。手术开始时，RIPC组血清IL-6、IL-8、IL-10、TNF-α、LDH、CK和TnI浓度高于对照组。术后，RIPC组细胞因子释放和心脏酶泄漏减弱；在一些但并非所有术后时间点，RIPC组细胞因子和心脏酶的血清浓度较低。此外，RIPC组冠状窦静脉MDA浓度较低，SOD浓度较高。同样，RIPC组心肌细胞中HSP 70的表达上调。肢体RIPC可安全、简便地应用于婴儿，可减轻全身炎症反应综合征，并可提高全身对IRI的耐受性，对心肌和肺IRI具有保护作用。HSP 70的表达在RIPC的作用机制中起重要作用。
