Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Basic Res Cardiol. 2016 Mar;111(2):10. doi: 10.1007/s00395-016-0529-6. Epub 2016 Jan 14.
Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.
远程缺血预处理（rIPC）通过短暂肢体缺血和再灌注（IR）循环诱导，具有心脏保护作用。目前尚未确定最佳的 rIPC 方案。我们研究了循环次数和每个 rIPC 循环中缺血持续时间的影响，以及效应器官质量对心脏保护效果的影响。此外，还研究了 rIPC 早期保护的持续时间。使用腹股沟水平的止血带，我们使 C57Bl/6NTac 小鼠经历间歇性后肢缺血和再灌注。rIPC 方案包括：（I）两个、四个、六个或八个循环，（II）每个循环中 2 分钟、5 分钟或 10 分钟的缺血，（III）单次或两次后肢闭塞，以及（IV）rIPC 与指数性心脏缺血之间 0.5、1.5、2.0 或 2.5 小时的间隔。所有 rIPC 方案后均进行 5 分钟再灌注。随后，将心脏暴露于体外 Langendorff 模型中的 25 分钟整体缺血和 60 分钟再灌注中。通过梗塞面积和缺血后血流动力学恢复来评估心脏保护作用。四到六个 rIPC 循环可提供显著的心脏保护作用，八个循环则不再提供进一步的保护。持续 2 分钟的缺血循环提供了与持续 5 分钟缺血的循环相同的保护作用，而延长至 10 分钟的循环则消除了保护作用。单次和两次后肢预处理具有同等的保护作用。在我们的小鼠模型中，rIPC 的保护持续时间为 1.5 小时。这些发现表明，rIPC 的循环次数和持续时间而不是暴露于 rIPC 的组织质量决定了 rIPC 的效果。
