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As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial ischaemia/reperfusion injury.", "subjects" : [ { "otype" : "Classification", "mtid" : 12125, "link" : "/api/classification/12125", "label" : "Általános orvostudomány", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 10545, "link" : "/api/classification/10545", "label" : "Biológiai tudományok", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 12215, "link" : "/api/classification/12215", "label" : "Klinikai orvostan", "published" : true, "snippet" : true } ], "digital" : true, "printed" : true, "sourceYear" : 2017, 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Moran, A.E., Forouzanfar, M.H., Roth, G.A., Mensah, G.A., Ezzati, M., Flaxman, A., Murray, C.J., Naghavi, M., The global burden of ischemic heart disease in 1990 and 2010: The Global Burden of Disease 2010 study Circulation, 129, pp. 1493-1501", "listPosition" : 3, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214269, "link" : "/api/reference/2214269", "label" : "4. Cung, T.T., Morel, O., Cayla, G., Rioufol, G., Garcia-Dorado, D., Angoulvant, D., Bonnefoy-Cudraz, E., Ovize, M., Cyclosporine before PCI in patients with acute myocardial infarction N Engl J Med, 373, pp. 1021-1031", "listPosition" : 4, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214270, "link" : "/api/reference/2214270", "label" : "5. Kolte, D., Khera, S., Aronow, W.S., Mujib, M., Palaniswamy, C., Sule, S., Jain, D., Fonarow, G.C., Trends in incidence, management, and outcomes of cardiogenic shock complicating ST-elevation myocardial infarction in the United States J Am Heart Assoc, 3, p. e000590", "listPosition" : 5, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214271, "link" : "/api/reference/2214271", "label" : "6. Thielmann, M., Sharma, V., Al-Attar, N., Bulluck, H., Bisleri, G., Bunge, J., Czerny, M., Hausenloy, D.J., ESC Joint Working Groups on Cardiovascular Surgery and the Cellular Biology of the Heart Position Paper: Peri-operative myocardial injury and infarction in patients undergoing CABG surgery Eur Heart J, , in revision", "listPosition" : 6, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214272, "link" : "/api/reference/2214272", "label" : "7. Hausenloy, D.J., Candilio, L., Evans, R., Ariti, C., Jenkins, D.P., Kolvekar, S., Knight, R., Yellon, D.M., Remote ischemic preconditioning and outcomes of cardiac surgery N Engl J Med, 373, pp. 1408-1417", "listPosition" : 7, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214273, "link" : "/api/reference/2214273", "label" : "8. Heusch, G., Libby, P., Gersh, B., Yellon, D., Bohm, M., Lopaschuk, G., Opie, L., Cardiovascular remodelling in coronary artery disease and heart failure Lancet, 383, pp. 1933-1943", "listPosition" : 8, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214274, "link" : "/api/reference/2214274", "label" : "9. Verhoef, T.I., Morris, S., Mathur, A., Singer, M., Potential economic consequences of a cardioprotective agent for patients with myocardial infarction: Modelling study BMJ Open, 5, p. e008164", "listPosition" : 9, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214275, "link" : "/api/reference/2214275", "label" : "10. Murry, C.E., Jennings, R.B., Reimer, K.A., Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium Circulation, 74, pp. 1124-1136", "listPosition" : 10, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214276, "link" : "/api/reference/2214276", "label" : "11. Marber, M.S., Latchman, D.S., Walker, J.M., Yellon, D.M., Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction Circulation, 88, pp. 1264-1272", "listPosition" : 11, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214277, "link" : "/api/reference/2214277", "label" : "12. Kuzuya, T., Hoshida, S., Yamashita, N., Fuji, H., Oe, H., Hori, M., Kamada, T., Tada, M., Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia Circ Res, 72, pp. 1293-1299", "listPosition" : 12, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214278, "link" : "/api/reference/2214278", "label" : "13. Na, H.S., Kim, Y.I., Yoon, Y.W., Han, H.C., Nahm, S.H., Hong, S.K., Ventricular premature beat-driven intermittent restoration of coronary blood flow reduces the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia Am Heart J, 132, pp. 78-83", "listPosition" : 13, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214279, "link" : "/api/reference/2214279", "label" : "14. Zhao, Z.Q., Corvera, J.S., Halkos, M.E., Kerendi, F., Wang, N.P., Guyton, R.A., Vinten-Johansen, J., Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning Am J Physiol Heart Circ Physiol, 285, pp. H579-H588", "listPosition" : 14, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214280, "link" : "/api/reference/2214280", "label" : "15. Przyklenk, K., Bauer, B., Ovize, M., Kloner, R.A., Whittaker, P., Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion Circulation, 87, pp. 893-899", "listPosition" : 15, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214281, "link" : "/api/reference/2214281", "label" : "16. Schwartz-Longacre, L., Kloner, R.A., Arai, A.E., Baines, C.P., Bolli, R., Braunwald, E., Downey, J., Yellon, D.M., New horizons in cardioprotection: Recommendations from the 2010 national heart, lung, and blood institute workshop Circulation, 124, pp. 1172-1179", "listPosition" : 16, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214282, "link" : "/api/reference/2214282", "label" : "17. Ovize, M., Baxter, G.F., Di Lisa, F., Ferdinandy, P., Garcia-Dorado, D., Hausenloy, D.J., Heusch, G., Schulz, R., Postconditioning and protection from reperfusion injury: Where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology Cardiovasc Res, 87, pp. 406-423", "listPosition" : 17, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214283, "link" : "/api/reference/2214283", "label" : "18. Hausenloy, D.J., Erik, B.H., Condorelli, G., Ferdinandy, P., Garcia-Dorado, D., Heusch, G., Lecour, S., Ovize, M., Translating cardioprotection for patient benefit: Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology Cardiovasc Res, 98, pp. 7-27", "listPosition" : 18, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214284, "link" : "/api/reference/2214284", "label" : "19. Lecour, S., Botker, H.E., Condorelli, G., Davidson, S.M., Garcia-Dorado, D., Engel, F.B., Ferdinandy, P., Hausenloy, D.J., ESC working group cellular biology of the heart: Position paper: Improving the preclinical assessment of novel cardioprotective therapies Cardiovasc Res, 104, pp. 399-411", "listPosition" : 19, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214285, "link" : "/api/reference/2214285", "label" : "20. Heusch, G., Cardioprotection: Chances and challenges of its translation to the clinic Lancet, 381, pp. 166-175", "listPosition" : 20, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214286, "link" : "/api/reference/2214286", "label" : "21. Heusch, G., Rassaf, T., Time to give up on cardioprotection? A critical appraisal of clinical studies on ischemic pre-, post-, and remote conditioning Circ Res, 119, pp. 676-695", "listPosition" : 21, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214287, "link" : "/api/reference/2214287", "label" : "22. Meybohm, P., Bein, B., Brosteanu, O., Cremer, J., Gruenewald, M., Stoppe, C., Coburn, M., Zacharowski, K., A multicenter trial of remote ischemic preconditioning for heart surgery N Engl J Med, 373, pp. 1397-1407", "listPosition" : 22, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214288, "link" : "/api/reference/2214288", "label" : "23. Ottani, F., Latini, R., Staszewsky, L., La Locuratolo, V.L.N., Sicuro, M., Masson, S., Barlera, S., Limbruno, U., Cyclosporine A in reperfused myocardial infarction: The multicenter, controlled, open-label CYCLE trial J Am Coll Cardiol, 67, pp. 365-374", "listPosition" : 23, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214289, "link" : "/api/reference/2214289", "label" : "24. Heusch, G., Gersh, B.J., The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: A continual challenge Eur Heart J, 38, pp. 774-784", "listPosition" : 24, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214290, "link" : "/api/reference/2214290", "label" : "25. Olafsson, B., Forman, M.B., Puett, D.W., Pou, A., Cates, C.U., Friesinger, G.C., Virmani, R., Reduction of reperfusion injury in the canine preparation by intracoronary adenosine: Importance of the endothelium and the no-reflow phenomenon Circulation, 76, pp. 1135-1145", "listPosition" : 25, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214291, "link" : "/api/reference/2214291", "label" : "26. Goto, M., Miura, T., Iliodoromitis, E.K., O'Leary, E.L., Ishimoto, R., Yellon, D.M., Iimura, O., Adenosine infusion during early reperfusion failed to limit myocardial infarct size in a collateral deficient species Cardiovasc Res, 25, pp. 943-949", "listPosition" : 26, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214292, "link" : "/api/reference/2214292", "label" : "27. Ross, A.M., Gibbons, R.J., Stone, G.W., Kloner, R.A., Alexander, R.W., 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, pp. 1775-1780", "listPosition" : 27, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214293, "link" : "/api/reference/2214293", "label" : "28. Kloner, R.A., Forman, M.B., Gibbons, R.J., Ross, A.M., Alexander, R.W., Stone, G.W., Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: The AMISTAD-2 trial Eur Heart J, 27, pp. 2400-2405", "listPosition" : 28, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214294, "link" : "/api/reference/2214294", "label" : "29. Garcia-Dorado, D., Garcia-Del-Blanco, B., Otaegui, I., Rodriguez-Palomares, J., Pineda, V., Gimeno, F., Ruiz-Salmeron, R., Ferreira-Gonzalez, I., Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: A randomized controlled clinical trial Int J Cardiol, 177, pp. 935-941", "listPosition" : 29, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214295, "link" : "/api/reference/2214295", "label" : "30. Bulluck, H., Sirker, A., Loke, Y.K., Garcia-Dorado, D., Hausenloy, D.J., Clinical benefit of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials Int J Cardiol, 202, pp. 228-237", "listPosition" : 30, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214296, "link" : "/api/reference/2214296", "label" : "31. Yang, X.M., Philipp, S., Downey, J.M., Cohen, M.V., Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts Basic Res Cardiol, 101, pp. 311-318", "listPosition" : 31, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214297, "link" : "/api/reference/2214297", "label" : "32. Kitakaze, M., Asakura, M., Kim, J., Shintani, Y., Asanuma, H., Hamasaki, T., Seguchi, O., Kitamura, S., Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials Lancet, 370, pp. 1483-1493", "listPosition" : 32, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214298, "link" : "/api/reference/2214298", "label" : "33. Sonne, D.P., Engstrom, T., Treiman, M., Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart Regul Pept, 146, pp. 243-249", "listPosition" : 33, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214299, "link" : "/api/reference/2214299", "label" : "34. Timmers, L., Henriques, J.P., De Kleijn, D.P., Devries, J.H., Kemperman, H., Steendijk, P., Verlaan, C.W., Hoefer, I.E., Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury J Am Coll Cardiol, 53, pp. 501-510", "listPosition" : 34, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214300, "link" : "/api/reference/2214300", "label" : "35. Hausenloy, D.J., Yellon, D.M., Taking lizard saliva to heart Eur Heart J, 33, pp. 1426-1430", "listPosition" : 35, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214301, "link" : "/api/reference/2214301", "label" : "36. Lonborg, J., Vejlstrup, N., Kelbaek, H., Botker, H.E., Kim, W.Y., Mathiasen, A.B., Jorgensen, E., Engstrom, T., Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction Eur Heart J, 33, pp. 1491-1499", "listPosition" : 36, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214302, "link" : "/api/reference/2214302", "label" : "37. Woo, J.S., Kim, W., Ha, S.J., Kim, J.B., Kim, S.J., Kim, W.S., Seon, H.J., Kim, K.S., 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, pp. 2252-2260", "listPosition" : 37, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214303, "link" : "/api/reference/2214303", "label" : "38. Lonborg, J., Kelbaek, H., Vejlstrup, N., Botker, H.E., Kim, W.Y., Holmvang, L., Jorgensen, E., Engstrom, T., Exenatide reduces final infarct size in patients with STsegment-elevation myocardial infarction and short-duration of ischemia Circ Cardiovasc Interv, 5, pp. 288-295", "listPosition" : 38, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2214304, "link" : "/api/reference/2214304", "label" : "39. 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