远隔缺血适应在缺血性脑血管疾病中的应用研究进展
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摘要
远隔缺血适应(RIC)是一种新的缺血适应方式,通过远隔器官短暂的缺血-再灌注,以保护靶器官持续缺血性损伤,其常用方式是通过前臂的缺血(即骨骼肌缺血)为靶器官提供缺血保护,现已逐渐应用于缺血性心脑血管疾病的临床研究。RIC可降低缺血性脑血管疾病的发生率,改善缺血性脑血管疾病的预后,但有部分研究结果未提示有效。作者通过复习文献,对RIC的可能机制及其应用研究进行综述,以期为临床应用提供帮助。
Remote ischemic conditioning( RIC) is a new protective management for ischemia. By conferring brief episodes of ischemia with reperfusion for remote tissue,target organs are endowed with better resistance against ischemic injury. One of the most common methods is creating forearm ischemiareperfusion to protect other organs. Nowadays,RIC was tested in many clinical trials on ischemic cerebrovascular and cardiovascular diseases. M any of them showed that RIC could decrease the incidence of ischem ic cerebrovascular disease,and improve the prognosis. But there were still some negative trials. The authors reviewed the literature and summarized the possible mechanisms and relavent researches,aiming to provide a useful reference for clinical application.
Remote ischemic conditioning( RIC) is a new protective management for ischemia. By conferring brief episodes of ischemia with reperfusion for remote tissue,target organs are endowed with better resistance against ischemic injury. One of the most common methods is creating forearm ischemiareperfusion to protect other organs. Nowadays,RIC was tested in many clinical trials on ischemic cerebrovascular and cardiovascular diseases. M any of them showed that RIC could decrease the incidence of ischem ic cerebrovascular disease,and improve the prognosis. But there were still some negative trials. The authors reviewed the literature and summarized the possible mechanisms and relavent researches,aiming to provide a useful reference for clinical application.
引文
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[4]Przyklenk K.Reduction of myocardial infarct size with schemic"conditioning":physiologic and technical considerations[J].Anesth Analg,2013,117(4):891-901.
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[7]Zhao W,Meng R,Ma C,et al.Safety and efficacy of remote ischemic preconditioning in patients with severe carotid artery stenosis before carotid artery stenting:a proof-of-concept,randomized controlled trial[J].Circulation,2017,135(14):1325-1335.
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[9]Hougaard KD,Hjort N,Zeidler D,et al.Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke:a randomized trial[J].Stroke,2014,45(1):159-167.
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[12]Zografos TA,Katritsis GD,Katritsis DG.Remote ischemic preconditioning reduces peri-procedural myocardial injury in elective percutaneous coronary intervention:a m eta-analysis[J].Int J Cardiol,2014,173(3):530-532.
[13]Davies WR,Brown AJ,Watson W,et al.Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention:the CRISP stent trial long-term follow-up[J].Circ Cardiovasc Interv,2013,6(3):246-251.
[14]Thielmann M,Kottenberg E,Kleinbongard P,et al.Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery:a single-centre randomised,double-blind,controlled trial[J].Lancet,2013,382(9892):597-604.
[15]Karuppasamy P,Chaubey S,Dew T,et al.Remote intermittent ischemia before coronary artery bypass graft surgery:a strategy to reduce injury and inflammation?[J].Basic Res Cardiol,2011,106(4):511-519.
[16]Weber C.Far from the heart:receptor cross-talk in remote conditioning[J].Nat Med,2010,16(7):760-762.
[17]Aimo A,Borrelli C,Giannoni A,et al.Cardioprotection by remote ischemic conditioning:mechanisms and clinical evidences[J].World J Cardiol,2015,7(10):621-632.
[18]Shimizu M,Tropak M,Diaz RJ,et al.Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium:evidence suggesting cross-species protection[J].Clin Sci(Lond),2009,117(5):191-200.
[19]Kanoria S,Jalan R,Seifalian AM,et al.Protocols and mechanisms for remote ischemic preconditioning:a novel method for reducing ischemia reperfusion injury[J].Transplantation,2007,84(4):445-458.
[20]Lim SY,Hausenloy DJ.Remote ischemic conditioning:from bench to bedside[J].Front Physiol,2012,3:27.
[21]Ren C,Yan Z,Wei D,et al.Limb remote ischemic postconditioning protects against focal ischemia in rats[J].Brain Res,2009,1288:88-94.
[22]Wei D,Ren C,Chen X,et al.The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke[J].PLo S One,2012,7(2):e30892.
[23]Konstantinov IE,Arab S,Kharbanda RK,et al.The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans[J].Physiol Genomics,2004,19(1):143-150.
[24]Shimizu M,Saxena P,Konstantinov IE,et al.Remote ischemic preconditioning decreases adhesion and selectively modifies functional responses of human neutrophils[J].J Surg Res,2010,158(1):155-161.
[25]Konstantinov IE,Arab S,Li J,et al.The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium[J].J Thorac Cardiovasc Surg,2005,130(5):1326-1332.
[26]Veighey K,Macallister RJ.Clinical applications of remote ischemic preconditioning[J].Cardiol Res Pract,2012,2012:620681.
[27]Ren C,Gao X,Steinberg GK,et al.Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning[J].Neuroscience,2008,151(4):1099-1103.
[28]Kharbanda RK,Mortensen UM,White PA,et al.Transient limb ischemia induces remote ischemic preconditioning in vivo[J].Circulation,2002,106(23):2881-2883.
[29]Schmidt MR,Smerup M,Konstantinov IE,et al.Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism:first demonstration of remote ischemic perconditioning[J].Am J Physiol Heart Circ Physiol,2007,292(4):H1883-H1890.
[30]Hoda MN,Siddiqui S,Herberg S,et al.Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke[J].Stroke,2012,43(10):2794-2799.
[31]Hess DC,Hoda MN,Bhatia K.Remote limb perconditioning[corrected]and postconditioning:will it translate into a promising treatment for acute stroke?[J].Stroke,2013,44(4):1191-1197.
[32]Sun J,Tong L,Luan Q,et al.Protective effect of delayed remote limb ischemic postconditioning:role of mitochondrial K(ATP)channels in a rat model of focal cerebral ischemic reperfusion injury[J].J Cereb Blood Flow Metab,2012,32(5):851-859.
[33]An MY,Li Y,Chen WH,et al.Effects of non-invasive remote ischemic conditioning on rehabilitation after myocardial infarction[J].Biochem Biophys Res Commun,2017,488(2):278-284.
[34]Meng R,Asmaro K,Meng L,et al.Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis[J].Neurology,2012,79(18):1853-1861.
[35]Prasad A,G9ssl M,Hoyt J,et al.Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis,inflammatory response,and circulating endothelial progenitor cell counts:a single center randomized sham controlled trial[J].Catheter Cardiovasc Interv,2013,81(6):930-936.
[36]Carrasco-Chinchilla F,Mu1oz-García AJ,Domínguez-Franco A,et al.Remote ischaemic postconditioning:does it protect against ischaemic damage in percutaneous coronary revascularisation?Randomised placebo-controlled clinical trial[J].Heart,2013,99(19):1431-1437.
[37]Sloth AD,Schmidt MR,Munk K,et al.Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention[J].Eur Heart J,2014,35(3):168-175.
[2]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.
[3]Gho BC,Schoemaker RG,van den Doel MA,et al.Myocardial protection by brief ischemia in noncardiac tissue[J].Circulation,1996,94(9):2193-2200.
[4]Przyklenk K.Reduction of myocardial infarct size with schemic"conditioning":physiologic and technical considerations[J].Anesth Analg,2013,117(4):891-901.
[5]Przyklenk K,Bauer B,Ovize M,et al.Regional ischemic‘preconditioning’protects remote virgin myocardium from subsequent sustained coronary occlusion[J].Circulation,1993,87(3):893-899.
[6]D'Ascenzo F,Moretti C,OmedèP,et al.Cardiac remote ischaemic preconditioning reduces periprocedural myocardial infarction for patients undergoing percutaneous coronary interventions:a meta-analysis of randomised clinical trials[J].Euro Intervention,2014,9(12):1463-1471.
[7]Zhao W,Meng R,Ma C,et al.Safety and efficacy of remote ischemic preconditioning in patients with severe carotid artery stenosis before carotid artery stenting:a proof-of-concept,randomized controlled trial[J].Circulation,2017,135(14):1325-1335.
[8]England TJ,Hedstrom A,O'Sullivan S,et al.RECAST(remote ischemic conditioning after stroke trial):a pilot randomized placebo controlled phaseⅡtrial in acute ischemic stroke[J].Stroke,2017,48(5):1412-1415.
[9]Hougaard KD,Hjort N,Zeidler D,et al.Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke:a randomized trial[J].Stroke,2014,45(1):159-167.
[10]Meng R,Ding Y,Asmaro K,et al.Ischemic conditioning is safe and effective for Octo-and nonagenarians in stroke prevention and treatment[J].Neurotherapeutics,2015,12(3):667-677.
[11]Pei H,Wu Y,Wei Y,et al.Remote ischemic preconditioning reduces perioperative cardiac and renal events in patients undergoing elective coronary intervention:a meta-analysis of11 randomized trials[J].PLo S One,2014,9(12):e115500.
[12]Zografos TA,Katritsis GD,Katritsis DG.Remote ischemic preconditioning reduces peri-procedural myocardial injury in elective percutaneous coronary intervention:a m eta-analysis[J].Int J Cardiol,2014,173(3):530-532.
[13]Davies WR,Brown AJ,Watson W,et al.Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention:the CRISP stent trial long-term follow-up[J].Circ Cardiovasc Interv,2013,6(3):246-251.
[14]Thielmann M,Kottenberg E,Kleinbongard P,et al.Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery:a single-centre randomised,double-blind,controlled trial[J].Lancet,2013,382(9892):597-604.
[15]Karuppasamy P,Chaubey S,Dew T,et al.Remote intermittent ischemia before coronary artery bypass graft surgery:a strategy to reduce injury and inflammation?[J].Basic Res Cardiol,2011,106(4):511-519.
[16]Weber C.Far from the heart:receptor cross-talk in remote conditioning[J].Nat Med,2010,16(7):760-762.
[17]Aimo A,Borrelli C,Giannoni A,et al.Cardioprotection by remote ischemic conditioning:mechanisms and clinical evidences[J].World J Cardiol,2015,7(10):621-632.
[18]Shimizu M,Tropak M,Diaz RJ,et al.Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium:evidence suggesting cross-species protection[J].Clin Sci(Lond),2009,117(5):191-200.
[19]Kanoria S,Jalan R,Seifalian AM,et al.Protocols and mechanisms for remote ischemic preconditioning:a novel method for reducing ischemia reperfusion injury[J].Transplantation,2007,84(4):445-458.
[20]Lim SY,Hausenloy DJ.Remote ischemic conditioning:from bench to bedside[J].Front Physiol,2012,3:27.
[21]Ren C,Yan Z,Wei D,et al.Limb remote ischemic postconditioning protects against focal ischemia in rats[J].Brain Res,2009,1288:88-94.
[22]Wei D,Ren C,Chen X,et al.The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke[J].PLo S One,2012,7(2):e30892.
[23]Konstantinov IE,Arab S,Kharbanda RK,et al.The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans[J].Physiol Genomics,2004,19(1):143-150.
[24]Shimizu M,Saxena P,Konstantinov IE,et al.Remote ischemic preconditioning decreases adhesion and selectively modifies functional responses of human neutrophils[J].J Surg Res,2010,158(1):155-161.
[25]Konstantinov IE,Arab S,Li J,et al.The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium[J].J Thorac Cardiovasc Surg,2005,130(5):1326-1332.
[26]Veighey K,Macallister RJ.Clinical applications of remote ischemic preconditioning[J].Cardiol Res Pract,2012,2012:620681.
[27]Ren C,Gao X,Steinberg GK,et al.Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning[J].Neuroscience,2008,151(4):1099-1103.
[28]Kharbanda RK,Mortensen UM,White PA,et al.Transient limb ischemia induces remote ischemic preconditioning in vivo[J].Circulation,2002,106(23):2881-2883.
[29]Schmidt MR,Smerup M,Konstantinov IE,et al.Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism:first demonstration of remote ischemic perconditioning[J].Am J Physiol Heart Circ Physiol,2007,292(4):H1883-H1890.
[30]Hoda MN,Siddiqui S,Herberg S,et al.Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke[J].Stroke,2012,43(10):2794-2799.
[31]Hess DC,Hoda MN,Bhatia K.Remote limb perconditioning[corrected]and postconditioning:will it translate into a promising treatment for acute stroke?[J].Stroke,2013,44(4):1191-1197.
[32]Sun J,Tong L,Luan Q,et al.Protective effect of delayed remote limb ischemic postconditioning:role of mitochondrial K(ATP)channels in a rat model of focal cerebral ischemic reperfusion injury[J].J Cereb Blood Flow Metab,2012,32(5):851-859.
[33]An MY,Li Y,Chen WH,et al.Effects of non-invasive remote ischemic conditioning on rehabilitation after myocardial infarction[J].Biochem Biophys Res Commun,2017,488(2):278-284.
[34]Meng R,Asmaro K,Meng L,et al.Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis[J].Neurology,2012,79(18):1853-1861.
[35]Prasad A,G9ssl M,Hoyt J,et al.Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis,inflammatory response,and circulating endothelial progenitor cell counts:a single center randomized sham controlled trial[J].Catheter Cardiovasc Interv,2013,81(6):930-936.
[36]Carrasco-Chinchilla F,Mu1oz-García AJ,Domínguez-Franco A,et al.Remote ischaemic postconditioning:does it protect against ischaemic damage in percutaneous coronary revascularisation?Randomised placebo-controlled clinical trial[J].Heart,2013,99(19):1431-1437.
[37]Sloth AD,Schmidt MR,Munk K,et al.Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention[J].Eur Heart J,2014,35(3):168-175.