Novel Cardioprotective and Regenerative Therapies in Acute Myocardial Infarction: A Review of Recent and Ongoing Clinical Trials

References

• World Health Organization . Global status report on noncommunicable diseases 2014 . www.who.int/nmh/publications/ncd-status-report-2014/en/ .
   Google Scholar
• Acute myocardial infarction in patients presenting with ST-segment elevation (management of) ESC Clinical Practice Guidelines . Eur. Heart J.33, 2569 – 2619 ( 2012 ).
   PubMedGoogle Scholar
• Acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation (management of) ESC Clinical Practice Guidelines . Eur. Heart J.doi:https://doi.org/10.1093/eurheartj/ehv320 ( 2015 ) ( Epub ahead of print ).
   Google Scholar
• ESC/EACTS guidelines in myocardial revascularisation (Guidelines for) ESC Clinical Practice Guidelines . Eur. Heart J. doi:10.1093/eurheartj/ehu278 ( 2014 ) ( Epub ahead of print ).
   Google Scholar
• Acute and chronic heart failure ESC Clinical Practice Guidelines . Eur. Heart J.33, 1787 – 1847 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov . https://clinicaltrials.gov/ .
   Google Scholar
• Hausenloy DJ , YellonDM . Ischaemic conditioning and reperfusion injury . Nat. Rev. Cardiol.13 ( 4 ), 193 – 209 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Carden DL , GrangerDN . Pathophysiology of ischaemia-reperfusion injury . J. Pathol.190 ( 3 ), 255 – 266 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Park JL , LucchesiBR . Mechanisms of myocardial reperfusion injury . Ann. Thorac. Surg.68 ( 5 ), 1905 – 1912 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Kroemer G , GalluzziL, BrennerC . Mitochondrial membrane permeabilization in cell death . Physiol. Rev.87 ( 1 ), 99 – 163 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Cellier L , TamareilleS, KalakechHet al. Remote ischemic conditioning influences mitochondrial dynamics . Shock45 ( 2 ), 192 – 197 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Murry CE , JenningsRB, ReimerKA . Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium . Circulation74 ( 5 ), 1124 – 1136 ( 1986 ).
   PubMed Web of Science ®Google Scholar
• Yellon DM , DowneyJM . Preconditioning the myocardium: from cellular physiology to clinical cardiology . Physiol. Rev.83, 1113 – 1151 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Heusch G . Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning . Circ. Res.116, 674 – 699 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ . Cardioprotection techniques: preconditioning postconditioning and remote conditioning (basic science) . Curr. Pharm. Design.19, 4544 – 4563 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Przyklenk K , BauerB, OvizeM, KlonerRA, WhittakerP . Regional ischemic “preconditioning” protects remote virgin myocardium from subsequent sustained coronary occlusion . Circulation87 ( 3 ), 893 – 899 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Walsh SR , TangTY, KullarP, JenkinsDP, DutkaDP, GauntME . Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials . Eur. J. Cardiothorac. Surg.34, 985 – 994 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Healy DA , CarrollPJ, MoloneyMCet al. Systematic review and meta-analysis of remote ischaemic preconditioning in percutaneous coronary intervention . IJC Metabolic Endocrine1 ( C ), 13 – 19 ( 2013 ).
   Google Scholar
• D’Ascenzo F , MorettiC, OmedèPet al. Cardiac remote ischaemic preconditioning reduces periprocedural myocardial infarction for patients undergoing percutaneous coronary interventions: a meta-analysis of randomised clinical trials . EuroIntervention9 ( 12 ), 1463 – 1471 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Pei H , WuY, WeiY, YangY, TengS, ZhangH . Remote ischemic preconditioning reduces perioperative cardiac and renal events in patients undergoing elective coronary intervention: a meta-analysis of randomized trials . PLoS ONE9 ( 12 ), e115500 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Hoole SP , HeckPM, SharplesLet al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study: a prospective, randomized control trial . Circulation119, 820 – 827 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ , CandilioL, EvansRet al. Remote ischemic preconditioning and outcomes of cardiac surgery . N. Eng. J. Med.373 ( 15 ), 1408 – 1417 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• B⊘tker HE , KharbandaR, SchmidtMRet al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial . Lancet375, 727 – 734 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• White SK , FrohlichGM, SadoDMet al. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction . JACC Cardiovasc. Interv.8, 178 – 188 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Zhao ZQ , CorveraJS, HalkosMEet al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. American Journal of Physiology . Heart Circ. Physiol.285 ( 2 ), H579 – H588 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Staat P , RioufolG, PiotCet al. Postconditioning the human heart . Circulation112 ( 14 ), 2143 – 2148 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Javadov SA , ClarkeS, DasM, GriffithsEJ, LimKHH, HalestrapAP . Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart . J. Physiol.549 ( Pt 2 ), 513 – 524 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Ma X , ZhangX, LiC, LuoM . Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction . J. Interv. Cardiol.19, 367 – 375 ( 2006 ).
   PubMedGoogle Scholar
• Yang XC , LiuY, WangLFet al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention . J. Invasive Cardiol.19, 424 – 430 ( 2007 ).
   PubMedGoogle Scholar
• Thibault H , PiotC, StaatPet al. Long-term benefit of postconditioning . Circulation117, 1037 – 1044 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Lonborg J , KelbaekH, VejlstrupNet al. Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance . Circ. Cardiovasc. Interv.3, 34 – 41 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Araszkiewicz A , GrygierM, PydaMet al. Postconditioning reduces enzymatic infarct size and improves microvascular reperfusion in patients with ST-segment elevation myocardial infarction . Cardiology129, 250 – 257 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Sorensson P , SalehN, BouvierFet al. Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction . Heart96, 1710 – 1715 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Tarantini G , FavarettoE, MarraMPet al. Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial . Int. J. Cardiol.162, 33 – 38 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Eitel I , StiermaierT, RommelKPet al. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial . Eur. Heart J.36, 3049 – 3057 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Dwyer NB , MikamiY, HillandDet al. No cardioprotective benefit of ischemic postconditioning in patients with ST-segment elevation myocardial infarction . J. Interv. Cardiol.26, 482 – 490 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Freixa X , BelleraN, Ortiz-PérezJTet al. Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention . Eur. Heart J.33, 103 – 112 ( 2012 ).
   PubMedGoogle Scholar
• Abdelnoor M , SandvenI, LimalanathanS, EritslandJ . Postconditioning in ST-elevation myocardial infarction: a systematic review, critical appraisal, and meta-analysis of randomized clinical trials . Vasc. Health Risk Manag.10, 477 – 491 ( 2014 ).
   PubMedGoogle Scholar
• H⊘fsten DE , KelbækH, HelqvistSet al. The third DANish study of optimal acute treatment of patients with ST-segment elevation myocardial infarction: ischemic postconditioning or deferred stent implantation versus conventional primary angioplasty and complete revascularization versus treatment of culprit lesion only: rationale and design of the DANAMI trial program . Am. Heart J.169 ( 5 ), 613 – 621 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Montecucco F , CarboneF, SchindlerTH . Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments . Eur. Heart J.37 ( 16 ), 1268 – 1283 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Piot C , CroisilleP, StaatPet al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction . N. Engl. J. Med.359 ( 5 ), 473 – 481 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Cung TT , MorelO, CaylaGet al. Cyclosporine before PCI in patients with acute myocardial infarction . N. Engl. J. Med.373, 1021 – 1103 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ottani F , LatiniR, StaszewskyLet al. Cyclosporine A in reperfused myocardial infarction . J. Am. Coll. Cardiol.67 ( 4 ), 365 – 374 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Ciclosporin to Reduce Reperfusion Injury in Primary PCI (CAPRI) . https://clinicaltrials.gov/ct2/show/NCT02390674 .
   Google Scholar
• Bułdak Ł , MachnikG, BułdakRJ, ŁabuzekK, BołdysA, BelowskiD . Exenatide (a GLP-agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner . Pharmacol. Rep.68 ( 2 ), 329 – 337 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Bose AK , MocanuMM, CarrRD, BrandCL, YellonDM . Glucagon-like peptide can directly protect the heart against ischemia/reperfusion injury . Diabetes54, 146 – 151 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Timmers L , HenriquesJP, de KleijnDPet al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury . J. Am. Coll. Cardiol.53, 501 – 510 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ , WhittingtonHJ, WynneAMet al. Dipeptidyl peptidase-inhibitors and GLP-reduce myocardial infarct size in a glucose-dependent manner . Cardiovasc. Diabetol.12 ( 1 ), 154 ( 2013 ).
   PubMedGoogle Scholar
• L⊘nborg J , KelbækH, VejlstrupNet al. Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia . Circ. Cardiovasc. Interv.5 ( 2 ), 288 – 295 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Bernink FJP , TimmersL, DiamantMet al. Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction: The EXAMI study . Int. J. Cardiol.167 ( 1 ), 289 – 290 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Woo JS , KimW, HaSJet al. Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study . Arterioscler. Thromb. Vasc. Biol.33 ( 9 ), 2252 – 2260 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kloner RA . Current state of clinical translation of cardioprotective agents for acute myocardial infarction . Circ. Res.113 ( 4 ), 451 – 463 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Mahaffey KW , PumaJA, BarbagelataNAet al. [for the AMISTAD Investigators]. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction results of a multicenter, randomized, placebo-controlled trial: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial . J. Am. Coll. Cardiol.34 ( 6 ), 1711 – 1720 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Ross AM , GibbonsRJ, StoneGW, KlonerRA, AlexanderRW . A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II) . J. Am. Coll. Cardiol.45 ( 11 ), 1775 – 1780 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Desmet W , BogaertJ, DuboisCet al. High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction . Eur. Heart J.32, 867 – 877 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Fokkema ML , VlaarPJ, VogelzangMet al. Effect of high-dose intracoronary adenosine administration during primary percutaneous coronary intervention in acute myocardial infarction: a randomized controlled trial . Circ. Cardiovasc. Interv.2, 323 – 329 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Nazir SA , KhanJ, MahmoudIZet al. Adenosine and sodium nitroprusside versus control for the attenuation of infarct size and microvascular obstruction: the REFLO-STEMI trial . J. Am. Coll. Cardiol.65 ( 10 ), A216 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Fordyce CB , GershBJ, StoneGW, GrangerCB . Novel therapeutics in myocardial infarction: targeting microvascular dysfunction and reperfusion injury . Trends Pharmacol. Sci.36 ( 9 ), 605 – 616 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Janssens S . Effects of nitric oxide for inhalation in myocardial infarction size (NOMI) . Presented at : European Society of Cardiology Congress . Barcelona, Spain, 1 September 2014 ( Abstract 4029 ). www.escardio.org/The-ESC/Press-Office/Press-releases/NOMI-Nitric-oxide-inhalation-in-heart-attack-patients-sends-mixed-messages-bu .
   Google Scholar
• Jones DA , AndiapenM, Van-EijlTJAet al. The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial . BMJ Open3 ( 4 ), e002813 – e002813 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lincoff AM , RoeM, AylwardPet al. Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI randomized controlled trial . Eur. Heart J.35 ( 37 ), 2516 – 2523 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Atar D , ArhedenH, BerdeauxAet al. Effect of intravenous TROas an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results . Eur. Heart J.36 ( 2 ), 112 – 119 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Gibson CM , GiuglianoRP, KlonerRAet al. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-on reperfusion injury in patients undergoing primary percutaneous coronary intervention . Eur. Heart J.37 ( 16 ), 1296 – 1303 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Bulluck H , YellonDM, HausenloyDJ . Reducing myocardial infarct size: challenges and future opportunities . Heart102 ( 5 ), 341 – 348 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Kitakaze M , AsakuraM, KimJet al. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials . Lancet370 ( 9597 ), 1483 – 1493 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Saito Y . Roles of atrial natriuretic peptide and its therapeutic use . J. Cardiol.56 ( 3 ), 262 – 270 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Matsue Y , KagiyamaN, YoshidaKet al. Carperitide is associated with increased in-hospital mortality in acute heart failure: a propensity score-matched analysis . J. Card. Fail.21 ( 11 ), 859 – 864 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Sasabuchi Y , YasunagaH, MatsuiH, LeforAK, FushimiK, SanuiM . Carperitide increases the need for renal replacement therapy after cardiovascular surgery . J. Cardiothorac. Vasc. Anesth.29 ( 6 ), 1426 – 1431 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Newby LK , MarberMS, MelloniCet al. Losmapimod, a novel pmitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised Phase trial . Lancet384 ( 9949 ), 1187 – 1195 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• O’Donoghue ML , GlaserR, AylwardPEet al. Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial . Am. Heart J.169 ( 5 ), 622.e6 – 630.e6 ( 2015 ).
   Web of Science ®Google Scholar
• Zeymer U , SuryapranataH, MonassierJPet al. The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardio-protective effects of eniporide in acute myocardial infarction (ESCAMI) trial . J. Am. Coll. Cardiol.38, 1644 – 1650 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Mentzer RM Jr , BartelsC, BolliRet al. EXPEDITION study investigators. Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study . Ann. Thorac Surg.85, 1261 – 1270 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kimura K , NakaoK, ShibataYet al. Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction . J. Cardiol.67 ( 4 ), 307 – 313 ( 2015 ).
   PubMedGoogle Scholar
• Atar D , PetzelbauerP, SchwitterJet al. Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction . J. Am. Coll. Cardiol.53 ( 8 ), 720 – 729 ( 2009 ).
   PubMedGoogle Scholar
• Leor J , TuviaS, GuettaVet al. Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine . J. Am. Coll. Cardiol.54, 1014 – 1023 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Zeymer U , RaoSV, KrucoffMWet al. PRESERVATION I: bioabsorbable cardiac matrix for the prevention of remodeling of the ventricle after large ST-segment elevation myocardial infarction . Presented at : European Society of Cardiology (ESC) Congress . London, UK, 29 August–2 September 2015 ( Abstract 6007 ).
   Google Scholar
• Götberg M , OlivecronaGK, EngblomHet al. Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size . BMC Cardiovasc. Disord.8, 7 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Erlinge D , GötbergM, GrinesCet al. A pooled analysis of the effect of endovascular cooling on infarct size in patients with ST-elevation myocardial infarction . EuroIntervention8, 1435 – 1440 ( 2013 ).
   PubMedGoogle Scholar
• Kanemoto S , MatsubaraM, NomaMet al. Mild hypothermia to limit myocardial ischemia-reperfusion injury: importance of timing . Ann. Thorac Surg.87, 157 – 163 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Stone GW , DixonSR, GrinesCLet al. Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials . Am. J. Cardiol.100 ( 9 ), 1370 – 1375 ( 2007 ).
   PubMedGoogle Scholar
• O’Neill WW . Cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction (COOLMI) . Presented at : Transcatheter Cardiovascular Therapeutics Session . Washington, DC, USA, 15–19 September 2003 .
   Google Scholar
• Götberg M , OlivecronaGK, KoulSet al. A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction . Circ. Cardiovasc. Interv.3, 400 – 407 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Erlinge D , GötbergM, LangIet al. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction . J. Am. Coll. Cardiol.63 ( 18 ), 1857 – 1865 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Nichol G , StricklandW, ShavelleDet al. Prospective, multicenter, randomized, con- trolled pilot trial of peritoneal hypothermia in patients with ST-segment-elevation myocardial infarction . Circ. Cardiovasc. Interv.8, e001965 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• O’Neill WW , MartinJL, DixonSRet al. Acute myocardial infarction with hyperoxemic therapy (AMIHOT) . J. Am. Coll. Cardiol.50 ( 5 ), 397 – 405 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Stone GW , MartinJL, de BoerMJet al. Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction . Circ. Cardiovasc. Interv.2 ( 5 ), 366 – 375 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Stub D , SmithK, BernardSet al. Air versus oxygen in ST-segment-elevation myocardial infarction . Circulation131 ( 24 ), 2143 – 2150 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• van de Hoef TP , NijveldtR, van der EnMet al. TCT-Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO) in acute ST-segment elevation myocardial infarction: final results of the prepare RAMSES study . J. Am. Coll. Cardiol.64 ( 11 ), B6 – B7 ( 2014 ).
   Google Scholar
• Satessa GD , LenjisaJL, GebremariamET, WolduMA . Stem cell therapy for myocardial infarction: challenges and prospects . J. Stem Cell Res. Ther.5 ( 3 ), 1 – 5 ( 2015 ).
   PubMedGoogle Scholar
• Naaijkens BA , van DijkA, KampOet al. Therapeutic application of adipose derived stem cells in acute myocardial infarction: lessons from animal models . Stem Cell Rev. Rep.10 ( 3 ), 389 – 398 ( 2014 ).
   PubMedGoogle Scholar
• Kim PJ , YangPC . Bone marrow cell therapy in clinical trials: a review of the literature . Rev. Recent Clin. Trials7 ( 3 ), 204 – 213 ( 2012 ).
   PubMedGoogle Scholar
• Asahara T , MuroharaT, SullivanAet al. Isolation of putative progenitor endothelial cells for angiogenesis . Science275, 964 – 967 ( 1997 ).
   PubMed Web of Science ®Google Scholar
• Asahara T , KawamotoA . Endothelial progenitor cells for postnatal vasculogenesis . Am. J. Physiol. Cell Physiol.287 ( 3 ), C572 – C579 ( 2004 ).
   PubMedGoogle Scholar
• Padfield GJ , NewbyDE, MillsNL . Understanding the role of endothelial progenitor cells in percutaneous coronary intervention . J. Am. Coll. Cardiol.55 ( 15 ), 1553 – 1565 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Tura O , SkinnerEM, BarclayGRet al. Late outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow . Stem Cells31 ( 2 ), 338 – 348 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Abdel-Latif A , BolliR, TleyjehIM . Adult bone marrow–derived cells for cardiac repair: a systematic review and meta-analysis . Arch. Intern. Med.167 ( 10 ), 989 – 997 ( 2007 ).
   PubMedGoogle Scholar
• Martin-Rendon E , BrunskillSJ, HydeCJ, StanworthSJ, MathurA, WattSM . Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review . Eur. Heart J.29 ( 15 ), 1807 – 1818 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Lipinski MJ , Biondi-ZoccaiGGL, AbbateAet al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials . J. Am. Coll. Cardiol.50 ( 18 ), 1761 – 1767 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Huikuri HV , KervinenK, NiemeläMet al. [for the FINCELL Investigators]. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction . Eur. Heart J.29, 2723 – 2732 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Meyer GP , WollertKC, LotzJet al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial . Circulation113, 1287 – 1294 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Leistner DM , Fischer-RasokatU, HonoldJet al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy . Clin. Res. Cardiol.100 ( 10 ), 925 – 934 ( 2011 ).
   PubMedGoogle Scholar
• Assmus B , LeistnerDM, SchächingerVet al. Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival . Eur. Heart J.35 ( 19 ), 1275 – 1283 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Hirsch A , NijveldtR, van der VleutenPAet al. Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial . Eur. Heart J.32 ( 14 ), 1736 – 1747 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Traverse JH , HenryTD, EllisSGet al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells to weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial . JAMA306 ( 19 ), 2110 – 2119 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Traverse JH , HenryTD, PepineCJet al. Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial . JAMA308, 2380 – 2389 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Suerder D , MankaR, TurchettoLet al. Intracoronary injection of bone marrow derived mononuclear cells, early or late after acute myocardial infarction: long-term effects on global left ventricular function – twelve months MRI and long-term clinical results of the SWISS-AMI trial . J. Am. Coll. Cardiol.64 ( S ), B45 ( 2014 ).
   Google Scholar
• de Jong R , HoutgraafJH, SamieiS, BoersmaE, DuckersHJ . Intracoronary stem cell infusion after acute myocardial infarction. A meta-analysis and update on clinical trials . Circ. Cardiovasc. Interv.7 ( 2 ), 156 – 167 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Nowbar AN , MielewczikM, KaravassilisMet al. Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis . BMJ348, g2688 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Williams AR , HareJM . Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease . Circ. Res.109 ( 8 ), 923 – 940 ( 2011 ).
   PubMedGoogle Scholar
• Hare JM , TraverseJH, HenryTDet al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction . J. Am. Coll. Cardiol.54, 2277 – 2286 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Chen SL , FangWW, YeFet al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction . Am. J. Cardiol.94, 92 – 95 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Patel AN , HenryTD, QuyyumiAAet al. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial . Lancet387 ( 10036 ), 2412 – 2421 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Chugh AR , BeacheGM, LoughranJHet al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance . Circulation126 ( 11 Suppl. 1 ), S54 – S64 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• The Lancet Editors . Expression of concern: the SCIPIO trial . Lancet383 ( 9925 ), 1279 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Cross M . Notice of retraction . Circulation129, e466 ( 2014 ).
   PubMedGoogle Scholar
• Malliaras K , MakkarRR, SmithRRet al. Intracoronary cardiosphere-derived cells after myocardial infarction . J. Am. Coll. Cardiol.63 ( 2 ), 110 – 122 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Golpanian S , SchulmanIH, EbertRFet al. Concise review: review and perspective of cell dosage and routes of administration from preclinical and clinical studies of stem cell therapy for heart disease . Stem Cells Transl. Med.5 ( 2 ), 186 – 191 ( 2015 ).
   PubMedGoogle Scholar
• Strauer BE , SteinhoffG . Cell therapy for acute myocardial infarction . In : Urgent Interventional Therapies . KipshidzeN ( Ed. ). John Wiley & Sons, Ltd, Chichester, UK, 497 – 501 ( 2014 ).
   Google Scholar
• Zhu H , JiangX, LiXet al. Intramyocardial delivery of VEGF via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction . Heart Vessels31 ( 6 ), 963 – 975 ( 2015 ).
   PubMedGoogle Scholar
• Kutryk MJB , StewartDJ . Use of gene modified stem cells for acute myocardial infarction . In : Stem Cell and Gene Therapy for Cardiovascular Disease . PerinEC, MillerLW, TaylorDA, WillersonJT ( Eds ). Academic Press, Boston, MA, USA, 417 – 432 ( 2015 ).
   Google Scholar
• Talan MI , AhmetI, LakattaEG . Did clinical trials in which erythropoietin failed to reduce acute myocardial infarct size miss a narrow therapeutic window?PLoS ONE7 ( 4 ), e34819 ( 2012 ).
   PubMedGoogle Scholar
• Roubille F , PrunierF, Barrere-LemaireSet al. What is the role of erythropoietin in acute myocardial infarct? Bridging the gap between experimental models and clinical trials . Cardiovasc. Drugs Ther.27 ( 4 ), 315 – 331 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Thakker R , YangP . Mesenchymal stem cell therapy for cardiac repair . Curr. Treat. Options Cardiovasc. Med.16 ( 7 ), 323 – 328 ( 2014 ).
   PubMedGoogle Scholar
• Drummond-Barbosa D . Stem cells, their niches and the systemic environment: an aging network . Genetics180 ( 4 ), 1787 – 1797 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Sahoo S , LosordoDW . Exosomes and cardiac repair after myocardial infarction . Circ. Res.114 ( 2 ), 333 – 344 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Singla DK . Stem cells and exosomes in cardiac repair . Curr. Opin. Pharmacol.27, 19 – 23 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Yu B , KimHW, GongMet al. Exosomes secreted from GATA-overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection . Int. J. Cardiol.182, 349 – 360 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Khan M , NickoloffE, AbramovaTet al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction . Circ. Res.117, 52 – 64 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Yang XM , LiuY, CuiLet al. Platelet P2Y12 blockers confer direct postconditioning-like protection in reperfused rabbit hearts . J. Cardiovasc. Pharmacol. Ther.18 ( 3 ), 251 – 262 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Bell RM , SivaramanV, KunuthurSP, CohenMV, DowneyJM, YellonDM . Cardioprotective properties of the platelet P2Y receptor inhibitor, cangrelor: protective in diabetics and reliant upon the presence of blood . Cardiovasc. Drugs Ther.29 ( 5 ), 415 – 418 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Marino M , RizzottiD, LeonardiS . Cangrelor: review of the drug and the CHAMPION programme (including PHOENIX) . Curr. Cardiol. Rep.16 ( 6 ), 493 ( 2014 ).
   PubMedGoogle Scholar
• ClinicalTrials Database: NCT02313961 . https://clinicaltrials.gov/ct2/show/NCT02313961 .
   Google Scholar
• ClinicalTrials Database: NCT01857414 . https://clinicaltrials.gov/ct2/show/NCT01857414 .
   Google Scholar
• ClinicalTrials Database: NCT02342522 . https://clinicaltrials.gov/ct2/show/NCT02342522 .
   Google Scholar
• ClinicalTrials Database: NCT01938235 . https://clinicaltrials.gov/ct2/show/NCT01938235 .
   Google Scholar
• ClinicalTrials Database: NCT02390674 . https://clinicaltrials.gov/ct2/show/NCT02390674 .
   Google Scholar
• ClinicalTrials Database: NCT01787110 . https://clinicaltrials.gov/ct2/show/NCT01787110 .
   Google Scholar