远程缺血后适应对心肌保护作用的研究进展
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摘要
急性ST段抬高型心肌梗死患者应尽早进行再灌注治疗,但梗死相关血管的再通可导致缺血再灌注损伤。目前,缺血预适应已逐渐演变为远程缺血后适应,其能减轻心肌缺血再灌注损伤,改善患者心功能、降低心力衰竭的风险,对早期心肌具有保护作用,但具体操作及临床效果仍面临许多问题,需要大量研究加以验证。远程缺血后适应的保护机制尚不清楚,相关研究尚无统一标准,可能与体液机制、神经反射机制或两者均有关。
Patients with acute ST-segment elevation myocardial infarction should be treated with reperfusion as soon as possible,but recanalization of infarct-related vessels leads to ischemia-reperfusion injury. At present,ischemic preconditioning has gradually evolved into remote ischemic postconditioning. Studies have shown that remote ischemic postconditioning can reduce myocardial ischemia-reperfusion injury,improve heart function,reduce the risk of heart failure,and protect myocardial cells at early stage. However,the specific operation and clinical effects still face many problems,which require a lot of research to verify. The protective mechanism of remote ischemic postconditioning is still unclear. Although related research has been emerging constantly,there is no uniform standard,which may be related to the humoral mechanism,the nervous reflex mechanism,or both.
Patients with acute ST-segment elevation myocardial infarction should be treated with reperfusion as soon as possible,but recanalization of infarct-related vessels leads to ischemia-reperfusion injury. At present,ischemic preconditioning has gradually evolved into remote ischemic postconditioning. Studies have shown that remote ischemic postconditioning can reduce myocardial ischemia-reperfusion injury,improve heart function,reduce the risk of heart failure,and protect myocardial cells at early stage. However,the specific operation and clinical effects still face many problems,which require a lot of research to verify. The protective mechanism of remote ischemic postconditioning is still unclear. Although related research has been emerging constantly,there is no uniform standard,which may be related to the humoral mechanism,the nervous reflex mechanism,or both.
引文
[1] Tu JV,Austin PC,Filate WA,et al. Outcomes of acute myocardialinfarction in Canada[J]. Can J Cardiol,2003,19(8):893-901.
[2] Merlocco AC,Redington KL,Disenhouse T,et al. Transcutaneouselectrical nerve stimulation as a novel method of remote precondi-tioning:In vitro validation in an animal model and first humanobservations[J]. Basic Res Cardiol,2014,109(3):406.
[3] Gross ER,Hsu AK,Urban TJ,et al. Nociceptive-induced myocar-dial remote conditioning is mediated by neuronal gamma proteinkinase C[J]. Basic Res Cardiol,2013,108(5):381.
[4] Murry CE,Jennings RB,Reimer KA. Preconditioning with ische-mia:A delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[5] Zhao ZQ,Corvera JS,Halkos ME,et al. Inhibition of myocardialinjury by ischemic postconditioning during reperfusion:Compari-son with ischemic preconditioning[J]. Am J Physiol Heart CircPhysiol,2003,285(2):H579-588.
[6] Kerendi F,Kin H,Halkos ME,et al. Remote postconditioning.Brief renal ischemia and reperfusion applied before coronaryartery reperfusion reduces myocardial infarct size via endogenousactivation of adenosine receptors[J]. Basic Res Cardiol,2005,100(5):404-412.
[7] Heusch G,B tker HE,Przyklenk K,et al. Remote ischemic condi-tioning[J]. J Am Coll Cardiol,2015,65(2):177-195.
[8] Prunier F,Angoulvant D,Saint Etienne C,et al. The RIPOST-MIstudy,assessing remote ischemic perconditioning alone or incombination with local ischemic postconditioning in ST-segmentelevation myocardial infarction[J]. Basic Res Cardiol,2014,109(2):400.
[9] Zhou C,Yao Y,Zheng Z,et al. Stenting technique,gender,andage are associated with cardioprotection by ischaemic postcondi-tioning in primary coronary intervention:A systematic review of 10randomized trials[J]. Eur Heart J,2012,33(24):3070-3077.
[10] Dickson EW,Reinhardt CP,Renzi FP,et al. Ischemic precondi-tioning may be transferable via whole blood transfusion:Prelimi-nary evidence[J]. J Thromb Thrombolysis,1999,8(2):123-129.
[11] Shimizu M,Tropak M,Diaz RJ,et al. Transient limb ischaemiaremotely preconditions through a humoral mechanism actingdirectly on the myocardium:Evidence suggesting cross-speciesprotection[J]. Clin Sci(Lond),2009,117(5):191-200.
[12] Tang ZL,Dai W,Li YJ,et al. Involvement of capsaicin-sensitivesensory nerves in early and delayed cardioprotection induced by abrief ischaemia of the small intestine[J]. Naunyn SchmiedebergsArch Pharmacol,1999,359(3):243-247.
[13] Hajrasouliha AR,Tavakoli S,Ghasemi M,et al. Endogenouscannabinoids contribute to remote ischemic preconditioning viacannabinoid CB2 receptors in the rat heart[J]. Eur J Pharmacol,2008,579(1/3):246-252.
[14] Pickard JM,B tker HE,Crimi G,et al. Remote ischemic condi-tioning:From experimental observation to clinical application:Report from the 8th Biennial Hatter Cardiovascular InstituteWorkshop[J]. Basic Res Cardiol,2015,110(1):453.
[15] Oldenburg O,Qin Q,Krieg T,et al. Bradykinin induces mitochon-drial ROS generation via NO,c GMP,PKG,and mito KATP chan-nel opening and leads to cardioprotection[J]. Am J Physiol HeartCirc Physiol,2004,286(1):H468-476.
[16]王保强,阚永丰,杨全会,等.肢体缺血预适应的肝保护作用与一氧化氮/内皮素-1系统关系的研究[J].中国应用生理学杂志,2010,26(3):376-379.
[17] Heusch G. Molecular mbasis of cardioprotection:Signal transduc-tion in ischemic pre-,post-,and remote conditioning[J]. CircRes,2015,116(4):674-699.
[18] Siddiqi N,Neil C,Bruce M,et al. Intravenous sodium nitrite inacute ST-elevation myocardial infarction:A randomized controlledtrial(NIAMI)[J]. Eur Heart J,2014,35(19):1255-1262.
[19] Tang YH,Xu JJ,Li JX,et al. Remote postconditioning induced bybrief pulmonary ischemia and reperfusion attenuates myocardialreperfusion injury in rabbits[J]. Chin Med J(Engl),2011,124(11):1683-1688.
[20] Sun T,Dong YH,Du W,et al. The role of microRNAs in myocardialinfarction:From molecular mechanism to clinical application[J]. IntJ Mol Sci,2017,18(4). pii:E745.
[21] Rohailla S,Clarizia N,Sourour M,et al. Acute,delayed and chro-nic remote ischemic conditioning is associated with downregula-tion of m TOR and enhanced autophagy signaling[J]. PLo S One,2014,9(10):e111291.
[22] Li J,Rohailla S,Gelber N,et al. MicroRNA-144 is a circulatingeffector of remote ischemic preconditioning[J]. Basic Res Cardiol,2014,109(5):423.
[23] Hausenloy DJ,Barrabes JA,Btker HE,et al. Ischaemic conditioningand targeting reperfusion injury:A 30 year voyage of discovery[J].Basic Res Cardiol,2016,111(6):70.
[24] Donato M,Buchholz B,Rodriguez M,et al. Role of the parasym-pathetic nervous system in cardioprotection by remote hindlimbischaemic preconditioning[J]. Exp Physiol,2013,98(2):425-434.
[25]彭长福,刘桂珍,鲁蓉,等.降钙素基因相关肽介导的预处理对溶血磷脂酰胆碱诱导的离体大鼠心肌损伤的保护作用[J].中国药理学与毒理学杂志,1998,12(2):81-84.
[26] Sharma R,Randhawa PK,Singh N,et al. Bradykinin in ischemicconditioning-induced tissue protection:Evidences and possiblemechanisms[J]. Eur J Pharmacol,2015,768:58-70.
[27] Qi W,Zhou F,Li S,et al. Remote ischemic postconditioning pro-tects ischemic brain from injury in rats with focal cerebral ische-mia/reperfusion associated with suppression of TLR4 and NF-κBexpression[J]. Neuro Report,2016,27(7):469-475.
[28] Chen GZ,Shan XY,Li XS,et al. Remote ischemic postcondition-ing protects the brain from focal ischemia/reperfusion injury byinhibiting autophagy through the m TOR/p70S6K pathway[J].Neurol Res,2018,40(3):182-188.
[29] Yang XM,Proctor JB,Cui L,et al. Multiple,brief coronary occlu-sions during early reperfusion protect rabbit hearts by targetingcell signaling pathways[J]. J Am Coll Cardiol,2004,44(5):1103-1110.
[30] Staat P,Rioufol G,Piot C,et al. Postconditioning the human heart[J].Circulation,2005,112(14):2143-2148.
[31] Brevoord D,Kranke P,Kuijpers M,et al. Remote ischemic condi-tioning to protect against ischemia-reperfusion injury:A systematicreview and meta-analysis[J]. PLo S One,2012,7(7):e42179.
[32] Pei H,Wu Y,Wei Y,et al. Remote ischemic preconditioningreduces perioperative cardiac and renal events in patients undergoing elective coronary intervention:A meta-analysis of 11 ran-domized trials[J]. PLo S One,2014,9(12):e115500.
[33] Bignami E,Landoni G,Crescenzi G,et al. Role of cardiac biomar-kers(troponin I and CK-MB)as predictors of quality of life andlong-term outcome after cardiac surgery[J]. Ann Card Anaesth,2009,12(1):22-26.
[34] Niu X,Zhang J,Chen D,et al. Remote ischaemic conditioning inpercutaneous coronary intervention:A meta-analysis of randomisedtrials[J]. Postepy Kardiol Interwencyjnej,2014,10(4):274-282.
[35] Liu Z,Wang YL,Hua Q,et al. Late remote ischemic precondition-ing provides benefit to patients undergoing elective percutaneouscoronary intervention[J]. Cell Biochem Biophys,2014,70(1):437-442.
[36] Eitel I,Stiermaier T,Rommel KP,et al. Cardioprotection by com-bined intrahospital remote ischaemic perconditioning and postcon-ditioning in ST-elevation myocardial infarction:The randomizedLipsia Conditioning trial[J]. Eur Heart J,2015,36(44):3049-3057.
[37] Le Page S,Bejan-Angoulvant T,Angoulvant D,et al. Remoteischemic conditioning and cardioprotection:A systematic reviewand meta-analysis of randomized clinical trials[J]. Basic ResCardiol,2015,110(2):11.
[38] Lnborg J,Kelbaek H,Vejlstrup N,et al. Cardioprotective effectsof ischaemic postconditioning in patients treated with primary per-cutaneous coronary intervention,evaluated by magnetic resonance[J].Circ Cardiovasc Interv,2010,3(1):34-41.
[39] Srensson P,Saleh N,Bouvier F,et al. Effect of postconditioning oninfarct size in patients with ST elevation myocardial infarction[J].Heart,2010,96(21):1710-1715.
[40] Ferdinandy P,Hausenloy DJ,Heusch G,et al. Interaction of riskfactors,comorbidities,and comedications with ischemia/reperfu-sion injury and cardioprotection by preconditioning,postcondition-ing,and remote conditioning[J]. Pharmacol Rev,2014,66(4):1142-1174.
[41] Manintveld OC,Te Lintel Hekkert M,van den Bos EJ,et al.Cardiac effects of postconditioning depend critically on the dura-tion of index ischemia[J]. Am J Physiol Heart Circ Physiol,2007,292(3):H1551-1560.
[42] Keeley EC,Boura JA,Grines CL,et al. Comparison of primary andfacilitated percutaneous coronary interventions for ST-elevationmyocardial infarction:Quantitative review of randomised trials[J].Lancet,2006,367(9510):579-588.
[43] Mc Leod SL,Iansavichene A,Cheskes S,et al. Remote ischemicperconditioning to reduce reperfusion injury during acuteST-segment-elevation myocardial infarction:A systematic reviewand Meta-analysis[J]. J Am Heart Assoc,2017,6(5):e005522.
[44] D'Ascenzo F,Moretti C,OmedèP,et al. Cardiac remote ischaemicpreconditioning reduces periprocedural myocardial infarction forpatients undergoing percutaneous coronary interventions:A meta-analysis of randomised clinical trials[J]. EuroIntervention,2014,9(12):1463-1471.
[2] Merlocco AC,Redington KL,Disenhouse T,et al. Transcutaneouselectrical nerve stimulation as a novel method of remote precondi-tioning:In vitro validation in an animal model and first humanobservations[J]. Basic Res Cardiol,2014,109(3):406.
[3] Gross ER,Hsu AK,Urban TJ,et al. Nociceptive-induced myocar-dial remote conditioning is mediated by neuronal gamma proteinkinase C[J]. Basic Res Cardiol,2013,108(5):381.
[4] Murry CE,Jennings RB,Reimer KA. Preconditioning with ische-mia:A delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[5] Zhao ZQ,Corvera JS,Halkos ME,et al. Inhibition of myocardialinjury by ischemic postconditioning during reperfusion:Compari-son with ischemic preconditioning[J]. Am J Physiol Heart CircPhysiol,2003,285(2):H579-588.
[6] Kerendi F,Kin H,Halkos ME,et al. Remote postconditioning.Brief renal ischemia and reperfusion applied before coronaryartery reperfusion reduces myocardial infarct size via endogenousactivation of adenosine receptors[J]. Basic Res Cardiol,2005,100(5):404-412.
[7] Heusch G,B tker HE,Przyklenk K,et al. Remote ischemic condi-tioning[J]. J Am Coll Cardiol,2015,65(2):177-195.
[8] Prunier F,Angoulvant D,Saint Etienne C,et al. The RIPOST-MIstudy,assessing remote ischemic perconditioning alone or incombination with local ischemic postconditioning in ST-segmentelevation myocardial infarction[J]. Basic Res Cardiol,2014,109(2):400.
[9] Zhou C,Yao Y,Zheng Z,et al. Stenting technique,gender,andage are associated with cardioprotection by ischaemic postcondi-tioning in primary coronary intervention:A systematic review of 10randomized trials[J]. Eur Heart J,2012,33(24):3070-3077.
[10] Dickson EW,Reinhardt CP,Renzi FP,et al. Ischemic precondi-tioning may be transferable via whole blood transfusion:Prelimi-nary evidence[J]. J Thromb Thrombolysis,1999,8(2):123-129.
[11] Shimizu M,Tropak M,Diaz RJ,et al. Transient limb ischaemiaremotely preconditions through a humoral mechanism actingdirectly on the myocardium:Evidence suggesting cross-speciesprotection[J]. Clin Sci(Lond),2009,117(5):191-200.
[12] Tang ZL,Dai W,Li YJ,et al. Involvement of capsaicin-sensitivesensory nerves in early and delayed cardioprotection induced by abrief ischaemia of the small intestine[J]. Naunyn SchmiedebergsArch Pharmacol,1999,359(3):243-247.
[13] Hajrasouliha AR,Tavakoli S,Ghasemi M,et al. Endogenouscannabinoids contribute to remote ischemic preconditioning viacannabinoid CB2 receptors in the rat heart[J]. Eur J Pharmacol,2008,579(1/3):246-252.
[14] Pickard JM,B tker HE,Crimi G,et al. Remote ischemic condi-tioning:From experimental observation to clinical application:Report from the 8th Biennial Hatter Cardiovascular InstituteWorkshop[J]. Basic Res Cardiol,2015,110(1):453.
[15] Oldenburg O,Qin Q,Krieg T,et al. Bradykinin induces mitochon-drial ROS generation via NO,c GMP,PKG,and mito KATP chan-nel opening and leads to cardioprotection[J]. Am J Physiol HeartCirc Physiol,2004,286(1):H468-476.
[16]王保强,阚永丰,杨全会,等.肢体缺血预适应的肝保护作用与一氧化氮/内皮素-1系统关系的研究[J].中国应用生理学杂志,2010,26(3):376-379.
[17] Heusch G. Molecular mbasis of cardioprotection:Signal transduc-tion in ischemic pre-,post-,and remote conditioning[J]. CircRes,2015,116(4):674-699.
[18] Siddiqi N,Neil C,Bruce M,et al. Intravenous sodium nitrite inacute ST-elevation myocardial infarction:A randomized controlledtrial(NIAMI)[J]. Eur Heart J,2014,35(19):1255-1262.
[19] Tang YH,Xu JJ,Li JX,et al. Remote postconditioning induced bybrief pulmonary ischemia and reperfusion attenuates myocardialreperfusion injury in rabbits[J]. Chin Med J(Engl),2011,124(11):1683-1688.
[20] Sun T,Dong YH,Du W,et al. The role of microRNAs in myocardialinfarction:From molecular mechanism to clinical application[J]. IntJ Mol Sci,2017,18(4). pii:E745.
[21] Rohailla S,Clarizia N,Sourour M,et al. Acute,delayed and chro-nic remote ischemic conditioning is associated with downregula-tion of m TOR and enhanced autophagy signaling[J]. PLo S One,2014,9(10):e111291.
[22] Li J,Rohailla S,Gelber N,et al. MicroRNA-144 is a circulatingeffector of remote ischemic preconditioning[J]. Basic Res Cardiol,2014,109(5):423.
[23] Hausenloy DJ,Barrabes JA,Btker HE,et al. Ischaemic conditioningand targeting reperfusion injury:A 30 year voyage of discovery[J].Basic Res Cardiol,2016,111(6):70.
[24] Donato M,Buchholz B,Rodriguez M,et al. Role of the parasym-pathetic nervous system in cardioprotection by remote hindlimbischaemic preconditioning[J]. Exp Physiol,2013,98(2):425-434.
[25]彭长福,刘桂珍,鲁蓉,等.降钙素基因相关肽介导的预处理对溶血磷脂酰胆碱诱导的离体大鼠心肌损伤的保护作用[J].中国药理学与毒理学杂志,1998,12(2):81-84.
[26] Sharma R,Randhawa PK,Singh N,et al. Bradykinin in ischemicconditioning-induced tissue protection:Evidences and possiblemechanisms[J]. Eur J Pharmacol,2015,768:58-70.
[27] Qi W,Zhou F,Li S,et al. Remote ischemic postconditioning pro-tects ischemic brain from injury in rats with focal cerebral ische-mia/reperfusion associated with suppression of TLR4 and NF-κBexpression[J]. Neuro Report,2016,27(7):469-475.
[28] Chen GZ,Shan XY,Li XS,et al. Remote ischemic postcondition-ing protects the brain from focal ischemia/reperfusion injury byinhibiting autophagy through the m TOR/p70S6K pathway[J].Neurol Res,2018,40(3):182-188.
[29] Yang XM,Proctor JB,Cui L,et al. Multiple,brief coronary occlu-sions during early reperfusion protect rabbit hearts by targetingcell signaling pathways[J]. J Am Coll Cardiol,2004,44(5):1103-1110.
[30] Staat P,Rioufol G,Piot C,et al. Postconditioning the human heart[J].Circulation,2005,112(14):2143-2148.
[31] Brevoord D,Kranke P,Kuijpers M,et al. Remote ischemic condi-tioning to protect against ischemia-reperfusion injury:A systematicreview and meta-analysis[J]. PLo S One,2012,7(7):e42179.
[32] Pei H,Wu Y,Wei Y,et al. Remote ischemic preconditioningreduces perioperative cardiac and renal events in patients undergoing elective coronary intervention:A meta-analysis of 11 ran-domized trials[J]. PLo S One,2014,9(12):e115500.
[33] Bignami E,Landoni G,Crescenzi G,et al. Role of cardiac biomar-kers(troponin I and CK-MB)as predictors of quality of life andlong-term outcome after cardiac surgery[J]. Ann Card Anaesth,2009,12(1):22-26.
[34] Niu X,Zhang J,Chen D,et al. Remote ischaemic conditioning inpercutaneous coronary intervention:A meta-analysis of randomisedtrials[J]. Postepy Kardiol Interwencyjnej,2014,10(4):274-282.
[35] Liu Z,Wang YL,Hua Q,et al. Late remote ischemic precondition-ing provides benefit to patients undergoing elective percutaneouscoronary intervention[J]. Cell Biochem Biophys,2014,70(1):437-442.
[36] Eitel I,Stiermaier T,Rommel KP,et al. Cardioprotection by com-bined intrahospital remote ischaemic perconditioning and postcon-ditioning in ST-elevation myocardial infarction:The randomizedLipsia Conditioning trial[J]. Eur Heart J,2015,36(44):3049-3057.
[37] Le Page S,Bejan-Angoulvant T,Angoulvant D,et al. Remoteischemic conditioning and cardioprotection:A systematic reviewand meta-analysis of randomized clinical trials[J]. Basic ResCardiol,2015,110(2):11.
[38] Lnborg J,Kelbaek H,Vejlstrup N,et al. Cardioprotective effectsof ischaemic postconditioning in patients treated with primary per-cutaneous coronary intervention,evaluated by magnetic resonance[J].Circ Cardiovasc Interv,2010,3(1):34-41.
[39] Srensson P,Saleh N,Bouvier F,et al. Effect of postconditioning oninfarct size in patients with ST elevation myocardial infarction[J].Heart,2010,96(21):1710-1715.
[40] Ferdinandy P,Hausenloy DJ,Heusch G,et al. Interaction of riskfactors,comorbidities,and comedications with ischemia/reperfu-sion injury and cardioprotection by preconditioning,postcondition-ing,and remote conditioning[J]. Pharmacol Rev,2014,66(4):1142-1174.
[41] Manintveld OC,Te Lintel Hekkert M,van den Bos EJ,et al.Cardiac effects of postconditioning depend critically on the dura-tion of index ischemia[J]. Am J Physiol Heart Circ Physiol,2007,292(3):H1551-1560.
[42] Keeley EC,Boura JA,Grines CL,et al. Comparison of primary andfacilitated percutaneous coronary interventions for ST-elevationmyocardial infarction:Quantitative review of randomised trials[J].Lancet,2006,367(9510):579-588.
[43] Mc Leod SL,Iansavichene A,Cheskes S,et al. Remote ischemicperconditioning to reduce reperfusion injury during acuteST-segment-elevation myocardial infarction:A systematic reviewand Meta-analysis[J]. J Am Heart Assoc,2017,6(5):e005522.
[44] D'Ascenzo F,Moretti C,OmedèP,et al. Cardiac remote ischaemicpreconditioning reduces periprocedural myocardial infarction forpatients undergoing percutaneous coronary interventions:A meta-analysis of randomised clinical trials[J]. EuroIntervention,2014,9(12):1463-1471.