Gedik Nilguen, Maciel Leonardo, Schulte Christiane, Skyschally Andreas, Heusch Gerd, Kleinbongard Petra
Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany.
Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen, Medical School, Essen, Germany; Laboratory of Cardiac Electrophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Arch Med Sci. 2017 Mar 1;13(2):448-458. doi: 10.5114/aoms.2016.61789. Epub 2016 Aug 16.
Remote ischemic preconditioning (RIPC) reduces myocardial infarct size, and protection can be transferred with plasma to other individuals, even across species. Mitochondria are the end-effectors of cardioprotection by local ischemic conditioning maneuvers. We have now analyzed mitochondrial function in response to RIPC.
Plasma from pigs undergoing placebo or RIPC (infarct size reduction by 67% in RIPC pigs compared to placebo) was transferred to isolated perfused rat hearts subjected to 30 min global ischemia followed by 120 min reperfusion for infarct size measurement. Additional experiments were terminated at 10 min reperfusion to isolate mitochondria for functional measurements. Effects of RIPC pig plasma were compared to local ischemic preconditioning (IPC) or to infusion of tumor necrosis factor α (TNF-α).
Ischemia/reperfusion (I/R) induced an infarct of 41 ±2% of total ventricular mass. Placebo pig plasma did not affect infarct size (38 ±1, = 0.13). The RIPC pig plasma reduced infarct size (27 ±2, < 0.001), as did IPC (20 ±1, < 0.001) and TNF-α (28 ±2, < 0.001). Associated with cardioprotection, reductions of mitochondrial adenosine diphosphate (ADP)-stimulated respiration, adenosine triphosphate (ATP) production and calcium retention capacity (CRC) by I/R and placebo pig plasma were prevented by RIPC pig plasma, as they were by IPC and TNF-α. Mitochondrial reactive oxygen species production (nmol HO/100 µg protein) induced by I/R (272 ±34) was comparable in response to placebo pig plasma (234 ±28, = 0.37) and was reduced by RIPC pig plasma (83 ±15, < 0.001) as well as by IPC (78 ±21, < 0.001) and TNF-α (125 ±42, = 0.002).
In rat myocardium, mitochondria are an intracellular target of protection induced by humoral factors retrieved from pigs undergoing RIPC.
远程缺血预处理（RIPC）可减小心肌梗死面积，且这种保护作用可通过血浆传递给其他个体，甚至跨物种传递。线粒体是局部缺血预处理操作诱导心脏保护的最终效应器。我们现在分析了RIPC对线粒体功能的影响。
将接受安慰剂或RIPC处理的猪（与安慰剂组相比，RIPC组猪的梗死面积减小了67%）的血浆转移至离体灌注的大鼠心脏，使其经历30分钟全心缺血，随后再灌注120分钟以测量梗死面积。另外的实验在再灌注10分钟时终止，分离线粒体进行功能测量。将RIPC组猪血浆的作用与局部缺血预处理（IPC）或肿瘤坏死因子α（TNF-α）输注的作用进行比较。
缺血/再灌注（I/R）导致梗死面积占心室总质量的41±2%。安慰剂组猪血浆对梗死面积无影响（38±1，P = 0.13）。RIPC组猪血浆减小了梗死面积（27±2，P < 0.001），IPC组（20±1，P < 0.001）和TNF-α组（28±2，P < 0.001）也有同样效果。与心脏保护相关的是，I/R和安慰剂组猪血浆导致的线粒体二磷酸腺苷（ADP）刺激的呼吸、三磷酸腺苷（ATP）生成以及钙保留能力（CRC）的降低被RIPC组猪血浆阻止，IPC组和TNF-α组也有同样效果。I/R诱导的线粒体活性氧生成（nmol HO/100 µg蛋白质）（272±34）在安慰剂组猪血浆作用下与之相当（234±28，P = 0.37），且被RIPC组猪血浆（83±15，P < 0.001）、IPC组（78±21，P < 0.001）和TNF-α组（125±42，P = 0.002）降低。
在大鼠心肌中，线粒体是从接受RIPC处理的猪体内提取的体液因子诱导的保护作用的细胞内靶点。
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