Bingöl Gizem, Jesurasa Steve, Stroethoff Martin, Jagdfeld Julian David, Henning Leila Sophie, Roth Sebastian, Lurati Buse Giovanna, M'Pembele René, Raupach Annika
Department of Anaesthesiology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
CARID, Cardiovascular Research Institute Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Front Cardiovasc Med. 2025 Aug 29;12:1631222. doi: 10.3389/fcvm.2025.1631222. eCollection 2025.
Remote ischemic preconditioning (RIPC) has been shown in several experimental studies as an organ protective procedure against ischemic injury, but the implementation of RIPC into routine clinical practice has so far failed due to contradictory study results. However, in order to identify patient groups that could benefit from RIPC, numerous clinical trials have been initiated, but only one study with patients undergoing heart transplantation (HTX). In HTX patients, RIPC appears to be cardioprotective when used immediately before surgery, while it has not been investigated whether the cardioprotective effect of RIPC is longer lasting. Therefore, this study assessed if a RIPC procedure prior to HTX has a cardioprotective potential in a later time window. To avoid masking a potential cardioprotective effect of RIPC in HTX patients by reduced susceptibility to cardioprotective signals due to comorbidities and medications in these patients, this study investigates the protective potential of this plasma in healthy young rats. Thus, male HTX patients were treated with a sham or a RIPC procedure (3 cycles with 5 min inflating/deflating) via a blood pressure cuff at the left upper limb prior surgery. After HTX, blood was collected at arrival on intensive care unit, 24 and 48 h post-surgery. The isolated plasma was transferred to isolated-perfused rat hearts before induction of ischemia/reperfusion injury. Cardiac function was determined by left ventricular pressure measurements and infarct size by triphenyltetrazolium chloride staining. In all measurements, no differences were observed between the sham- or RIPC plasma-treated groups at the respective time points. This suggests that RIPC plasma from HTX patients, at least in the experimental setup used, has no cardioprotective potential at later time points. This lack of effect could for instance be explained by either no or an insufficient amount of cardioprotective signals are produced or/and released into the blood following the RIPC procedure and needs to be explored in future studies.
远程缺血预处理（RIPC）在多项实验研究中已被证明是一种针对缺血性损伤的器官保护措施，但由于研究结果相互矛盾，RIPC至今未能应用于常规临床实践。然而，为了确定可能从RIPC中获益的患者群体，已经启动了大量临床试验，但仅有一项针对心脏移植（HTX）患者的研究。在HTX患者中，RIPC在手术前立即使用时似乎具有心脏保护作用，而RIPC的心脏保护作用是否具有更长的持续时间尚未得到研究。因此，本研究评估了HTX前的RIPC程序在稍后的时间窗内是否具有心脏保护潜力。为避免因这些患者的合并症和药物治疗导致对心脏保护信号的敏感性降低而掩盖RIPC在HTX患者中的潜在心脏保护作用，本研究在健康年轻大鼠中研究了这种血浆的保护潜力。因此，男性HTX患者在手术前通过左上肢血压袖带接受假手术或RIPC程序（3个循环，每次充气/放气5分钟）治疗。HTX后，在重症监护病房入院时、术后24小时和48小时采集血液。将分离出的血浆在诱导缺血/再灌注损伤前转移至离体灌注的大鼠心脏。通过左心室压力测量确定心脏功能，通过氯化三苯基四氮唑染色确定梗死面积。在所有测量中，假手术或RIPC血浆治疗组在各自时间点均未观察到差异。这表明，至少在所使用的实验设置中，HTX患者的RIPC血浆在稍后的时间点没有心脏保护潜力。例如，这种缺乏效应的原因可能是RIPC程序后没有产生或/和释放到血液中的心脏保护信号不足，这需要在未来的研究中进行探索。
