Research progress of remote ischemic postconditioning in ischemic vascular disease

doi:10.3760/cma.j.issn.1007-1245.2021.06.040

Abstract

Abstract: Remote ischemic postconditioning (RIPostC) refers to the ability to activate the endogenous protective mechanism of the body to reduce the ischemia-reperfusion injury of important organs by giving rapid and intermittent stimulation of limb blood flow interruption after reperfusion. Early reperfusion treatment is the main method for the treatment of ischemic vascular disease, but a large number of studies and clinical evidences show that the recovery of blood perfusion and oxygen supply of some ischemic tissues and organs aggravates the tissue damage, i.e. ischemia-reperfusion injury, including myocardial ischemia/reperfusion (I/R) injury, such as arrhythmia, myocardial systolic and diastolic dysfunction, metabolic abnormality, myocardial ultrastructural changes, and increased cerebral infarction area. Studies at home and abroad have found that remote ischemic postconditioning can reduce the reperfusion injury of heart, brain, kidney, and other important organs. In order to deal with the challenge of reducing reperfusion injury, remote ischemic postconditioning has become a hot topic in clinical research.

Key words: Remote ischemic post-conditioning, Ischemic vascular disease, Myocardial infarction, Cerebral infarction, Reducing reperfusion injury

摘要： 远隔缺血后适应(remote ischemic postconditioning,RIPostC)是指在再灌注后通过给予快速、间断性的肢体血流中断刺激,调动机体内源性保护机制以减轻重要器官缺血再灌注损伤的能力。早期再灌注治疗是缺血性血管病治疗的主要手段,但大量研究及临床证据表明:恢复某些缺血组织器官的血液灌注及氧供反而加重组织损伤即缺血-再灌注损伤,包括心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤如心律失常、心肌舒缩功能障碍、代谢异常以及心肌超微结构的改变及脑梗死面积增大等损伤。国内外研究发现远隔缺血后适应具有减轻心、脑、肾等重要器官再灌注损伤的作用。为应对减轻再灌注损伤这一挑战,远隔缺血后适应目前成为临床研究的热门话题。因此尽快恢复组织器官的血流灌注是缺血性血管病最为重要的治疗方案,其中包括溶栓治疗、经皮冠状动脉介入治疗等手段。但是恢复器官血流灌注后所致的再灌注损伤又是临床治疗的一大难题,其中心脏及脑对血流灌注及氧供需求高,极易发生缺血-再灌注损伤,因此探究减轻再灌注损伤成为了缺血性血管病研究热门话题。

关键词: 远隔缺血后适应, 缺血性血管病, 心肌梗死, 脑梗死, 减轻再灌注损伤

Zhang Yuanjie, Qu Fuzhen. Research progress of remote ischemic postconditioning in ischemic vascular disease[J]. International Medicine and Health Guidance News, 2021, 27(6): 941-944.

张元杰, 曲辅政. 远隔缺血后适应在缺血性血管病的研究进展[J]. 国际医药卫生导报, 2021, 27(6): 941-944.

References

[1] Kerendi F, Kin H, Halkos ME, et al.Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors[J]. Basic Res Cardiol, 2005, 100(5): 404-412. DOI: 10.1007/s00395-005-0539-2.
[2] Ren C, Yan Z, Wei D, et al.Limb remote ischemic postconditioning protects against focal ischemia in rats[J]. Brain Research, 2009, 1288: 88-94. DOI: 10.1016/j.brainres.2009.07.029.
[3] 殷莺, 邱洪, 杨向军, 等. 远程缺血后适应对急性ST段抬高型心肌梗死患者PCI治疗后的肾功能保护作用[J]. 岭南心血管病杂志, 2015, 21(5): 594-596, 631. DOI: 10.3969/j.issn.1007-9688.2015.05.003.
[4] Reimer KA, Murry CE, Yamasawa I, et al.Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis[J]. Am J Physiol, 1986, 251(6 Pt 2): H1306-1315. DOI: 10.1152/ajpheart.1986.251.6.H1306.
[5] Reimer KA, Lowe JE, Rasmusse MM.The Wavefront Phenomenon of Ischemic Cell Death: 1. Myocardial Infarct Size vs Duration of Coronary Occlusion in Dogs[J]. Circulation, 1977, 56(5): 786-794. DOI: 10.1161/01.cir.56.5.786.
[6] Jennings RB, Hawkins HK, Lowe JE, et al.Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog[J]. Am J Pathol, 1978, 92(1): 187-214.
[7] Murry CE, Jennings RB, Reimer KA.Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium[J]. Circulation, 1986, 74(5): 1124-1136. DOI: 10.1161/01.cir.74.5.1124.
[8] Suzuki S, Inaba K, Konno H.Ischemic preconditioning in hepatic ischemia and reperfusion[J]. Curr Opin Organ Transplant, 2008, 13(2): 142-147. DOI: 10.1097/MOT.0b013e3282f6a164.
[9] Yamada T, Nagata H, Kosugi S, et al.Interaction between anesthetic conditioning and ischemic preconditioning on metabolic function after hepatic ischemia-reperfusion in rabbits[J]. J Anesth, 2018, 32(4): 599-607. DOI: 10.1007/s00540-018-2523-7.
[10] Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol Heart Circ Physiol, 2003, 285(2): H579-H588. DOI: 10.1152/ajpheart.01064.2002.
[11] Kerendi F, Kin H, Halkos ME, et al.Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors[J]. Basic Research in Cardiology, 2005, 100(5): 404-412. DOI: 10.1007/s00395-005-0539-2.
[12] Bolli R, Patel BS, Jeroudi MO, et al.Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone[J]. J Clin Invest, 1988, 82(2): 476-485. DOI: 10.1172/JCI113621.
[13] Sun HY, Wang NP, Kerendi F, et al.Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J]. Am J Physiol Heart Circ Physiol, 2005, 288(4): H1900-H1908. DOI: 10.1152/ajpheart.01244.2003.
[14] Kin H, Zhao ZQ, Sun HY, et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004, 62(1): 74-85. DOI: 10.1016/j.cardiores.2004.01.006.
[15] Baxter GF.The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on[J]. Basic Res Cardiol, 2002, 97(4): 268-275. DOI: 10.1007/s00395-002-0366-7.
[16] Li CM, Zhang XH, Ma XJ, et al.Limb ischemic postconditioning protects myocardium from ischemia-reperfusion injury[J]. Scand Cardiovasc J, 2006, 40(5): 312-317. DOI: 10.1080/14017430600925292.
[17] Zhang JQ, Wang Q, Xue FS, et al.Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury[J]. Chin Med J(Engl), 2013, 126(20): 3949-3955.
[18] Tang YH, Xu JJ, Li JX, et al.Remote postconditioning induced by brief pulmonary ischemia and reperfusion attenuates myocardial reperfusion injury in rabbits[J]. Chin Med J (Engl), 2011, 124(11): 1683-1688.
[19] 任慧敏, 谢瑞芹, 崔炜, 等. 下肢骨骼肌缺血后处理对兔缺血/再灌注心肌坏死和凋亡的影响[J]. 中国应用生理学杂志, 2012, 28(4): 323-327.
[20] Yu Y, Jia XJ, Zong QF, et al.Remote ischemic postconditioning protects the heart by upregulating ALDH2 expression levels through the PI3K/Akt signaling pathway[J]. Mol Med Rep, 2014, 10(1): 536-542. DOI: 10.3892/mmr.2014.2156.
[21] Takagi H, Matsui Y, Sadoshima J.The Role of Autophagy in Mediating Cell Survival and Death During Ischemia and Reperfusion in the Heart[J]. Antioxid Redox Signal, 2007, 9(9): 1373-1382. DOI: 10.1089/ars.2007.1689.
[22] Matsui Y, Takagi H, Qu X, et al.Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion: Roles of AMP-Activated Protein Kinase and Beclin 1 in Mediating Autophagy[J]. Circ Res, 2007, 100(6): 914-922. DOI: 10.1161/01.RES.0000261924.76669.36.
[23] Han Z, Cao J, Song D, et al.Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice[J]. PloS One, 2014, 9(1): e86838. DOI: 10.1371/journal.pone.0086838.
[24] Hao M, Zhu S, Liang H, et al.Myocardial Ischemic Postconditioning Promotes Autophagy against Ischemia Reperfusion Injury via the Activation of the nNOS/AMPK/mTOR Pathway[J]. Int J Mol Sci, 2017, 18(3): 614. DOI: 10.3390/ijms18030614.
[25] Song Y, Shan JG, Xue Z, et al.Remote Postconditioning Induced by Trauma Protects the Mouse Heart against Ischemia Reperfusion Injury. Involvement of the Neural Pathway and Molecular Mechanisms[J]. Cardiovasc Drugs Ther, 2016, 30(3): 271-280. DOI: 10.1007/s10557-016-6661-6.
[26] Crimi G, Pica S, Raineri C, et al.Remote Ischemic Post-Conditioning of the Lower Limb During Primary Percutaneous Coronary Intervention Safely Reduces Enzymatic Infarct Size in Anterior Myocardial Infarction[J]. JACC: Cardiovasc Interv, 2013, 6(10): 1055-1063. DOI: 10.1016/j.jcin.2013.05.011.
[27] Stiermaier T, Jensen J, Rommel K, et al.Combined Intrahospital Remote Ischemic Perconditioning and Postconditioning Improves Clinical Outcome in ST-Elevation Myocardial Infarction[J]. Circ Res, 2019, 124(10): 1482-1491. DOI: 10.1161/CIRCRESAHA.118.314500.
[28] Wei M, Huo K, Liu R, et al.The Design and Rationale of a Clinical Trial Evaluating Limb Postconditioning in Young Patients with Intracranial Arterial Stenosis[J]. J Stroke Cerebrovasc Dis, 2016, 25(10): 2506-2512. DOI: 10.1016/j.jstrokecerebrovasdis.2016.06.027.
[29] 王心颖, 丁文婷, 鲍双振, 等. 远隔缺血后适应治疗对缺血性脑卒中患者神经功能保护作用的临床研究[J]. 中国全科医学, 2018, 21(18): 2163-2166. DOI: 10.3969/j.issn.1007-9572.2018.00.193.