Ischaemic and hypoxic conditioning: potential for protection of vital organs
Ischaemic and hypoxic conditioning: potential for protection of vital organs
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DOI：
10.1113/ep087122
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发表时间：
2019-03-01
影响因子：
2.7
通讯作者：
Rickards, Caroline A.
中科院分区：
文献类型：
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作者：
Sprick, Justin D.;Mallet, Robert T.;Rickards, Caroline A.
尽管有大量资源用于开发有效的治疗方法，但心肌梗塞和中风仍然是全世界死亡的主要原因。在本次研讨会报告中，我们强调了间歇性缺血和缺氧调理方案在对抗心脏和大脑缺血的有害后果方面的潜在应用。讨论了间歇性缺氧训练保护作用的机制，包括缺氧诱导因子 1 和 Nrf2 转录因子的激活、抗氧化剂和 ATP 生成酶的合成，以及小胶质细胞从促炎表型向抗炎表型的转变。尽管对于临床前模型中远程缺血预处理（RIPC）的功效几乎没有争议，但这种策略并没有一致地转化为临床领域。这种翻译的缺乏可能与迄今为止的目标患者群体以及两项主要 RIPC 临床试验中使用的麻醉方案有关。此外，我们还不完全了解 RIPC 保护重要器官的机制，并且合并症（例如高胆固醇血症、糖尿病）可能会干扰其疗效。最后，还进行了新的调整，将 RIPC 扩展到更长期的环境。其中一项改编是 RIPC 运动 (RIPC-X)，这是一种将周期性 RIPC 应用于血流限制运动 (BFRE) 的创新范例。最近的研究结果表明，这种新颖的运动方式减弱了夸张的血流动力学反应，这可能会限制传统 BFRE 在某些临床环境中的使用。总的来说，间歇性缺血和缺氧调节模式仍然是预防缺血性损伤的一个令人兴奋的前沿领域。
Myocardial infarction and stroke remain leading causes of death worldwide, despite extensive resources directed towards developing effective treatments. In this Symposium Report we highlight the potential applications of intermittent ischaemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischaemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training are discussed, including the activation of hypoxia-inducible factor-1 and Nrf2 transcription factors, synthesis of antioxidant and ATP-generating enzymes, and a shift in microglia from pro- to anti-inflammatory phenotypes. Although there is little argument regarding the efficacy of remote ischaemic preconditioning (RIPC) in pre-clinical models, this strategy has not consistently translated into the clinical arena. This lack of translation may be related to the patient populations targeted thus far, and the anaesthetic regimen used in two of the major RIPC clinical trials. Additionally, we do not fully understand the mechanism through which RIPC protects the vital organs, and co-morbidities (e.g. hypercholesterolemia, diabetes) may interfere with its efficacy. Finally, novel adaptations have been made to extend RIPC to more chronic settings. One adaptation is RIPC-exercise (RIPC-X), an innovative paradigm that applies cyclical RIPC to blood flow restriction exercise (BFRE). Recent findings suggest that this novel exercise modality attenuates the exaggerated haemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischaemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischaemic injuries.