Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile; Department of Internal Medicine, University of Chile Clinical Hospital, Chile.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile.
Med Hypotheses. 2018 Sep;118:146-150. doi: 10.1016/j.mehy.2018.07.002. Epub 2018 Jul 2.
Remote ischemic preconditioning (RIPC) is a cardioprotective strategy against myocardial damage by ischemia-reperfusion. Many in-vivo and ex-vivo animal researches have demonstrated that RIPC decreases significantly the ischemia-reperfusion myocardial damage, by up to 58% in isolated rat heart. Cardiac artery bypass graft surgery (CABG) is a clinical model of myocardial ischemia-reperfusion and a clinical potential application to RIPC. However, although RIPC has shown successful results in experimental studies, clinical trials on CABG have failed to demonstrate a benefit of RIPC in humans. Strikingly, the main proposed factors associated with this translational failure also impair the balance of the autonomic nervous system (ANS), which has shown to play a key role in RIPC cardioprotection in animal models. Comorbidities, chronic pharmacological treatment and anesthesic drugs - common conditions in CABG patients - cause an ANS imbalance through parasympathetic activity decrement. On the other hand, ANS and specially the parasympathetic branch are essentials to get cardioprotection by RIPC in animal models. Consequently, we propose that ANS imbalance in CABG patients would explain the failure of RIPC clinical trials. Whether our hypothesis is true, many patients could be benefited by RIPC: a cheap, simple and virtually broad-available cardioprotective maneuver. In this paper we discuss the evidence that support this hypothesis and its clinical implications.
远程缺血预处理 (RIPC) 是一种针对缺血再灌注心肌损伤的心脏保护策略。许多体内和体外动物研究表明，RIPC 可显著减少缺血再灌注引起的心肌损伤，在离体大鼠心脏中可减少多达 58%。冠状动脉旁路移植术 (CABG) 是心肌缺血再灌注的临床模型，也是 RIPC 的临床潜在应用。然而，尽管 RIPC 在实验研究中显示出成功的结果，但 CABG 的临床试验未能证明 RIPC 对人类有益。引人注目的是，与这种转化失败主要相关的因素也会破坏自主神经系统 (ANS) 的平衡，而自主神经系统在动物模型中对 RIPC 的心脏保护作用发挥着关键作用。合并症、慢性药物治疗和麻醉药物——CABG 患者的常见情况——通过降低副交感神经活动导致自主神经系统失衡。另一方面，自主神经系统，特别是副交感神经分支，是动物模型中通过 RIPC 获得心脏保护所必需的。因此，我们提出 CABG 患者的自主神经系统失衡会解释 RIPC 临床试验的失败。无论我们的假设是否正确，许多患者都可以从 RIPC 中受益：一种廉价、简单且几乎广泛可用的心脏保护手段。本文讨论了支持这一假设的证据及其临床意义。
