Skip to main content

Advertisement

SpringerLink
Log in

Reperfusion injury as a therapeutic challenge in patients with acute myocardial infarction

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Cardiomyocyte death secondary to transient ischemia occurs mainly during the first minutes of reperfusion, in the form of contraction band necrosis involving sarcolemmal rupture. Cardiomyocyte hypercontracture caused by re-energisation and pH recovery in the presence of impaired cytosolic Ca2+ control as well as calpain-mediated cytoskeletal fragility play prominent roles in this type of cell death. Hypercontracture can propagate to adjacent cells through gap junctions. More recently, opening of the mitochondrial permeability transition pore has been shown to participate in reperfusion-induced necrosis, although its precise relation with hypercontracture has not been established. Experimental studies have convincingly demonstrated that infarct size can be markedly reduced by therapeutic interventions applied at the time of reperfusion, including contractile blockers, inhibitors of Na+/Ca2+ exchange, gap junction blockers, or particulate guanylyl cyclase agonists. However, in most cases drugs for use in humans have not been developed and tested for these targets, while the effect of existing drugs with potential cardioprotective effect is not well established or understood. Research effort should be addressed to elucidate the unsolved issues of the molecular mechanisms of reperfusion-induced cell death, to identify and validate new targets and to develop appropriate drugs. The potential benefits of limiting infarct size in patients with acute myocardial infarction receiving reperfusion therapy are enormous.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world: global burden of disease study. Lancet 349:1269–1276

    PubMed  CAS  Google Scholar 

  2. Thompson PL, Fletcher EE, Katavatis V (1979) Enzymatic indices of myocardial necrosis: influence on short- and long-term prognosis after myocardial infarction. Circulation 59:113–119

    PubMed  CAS  Google Scholar 

  3. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB (1977) The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 56:786–794

    PubMed  CAS  Google Scholar 

  4. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. (1987) Intravenous streptokinase given within 0–4 hours of onset of myocardial infarction reduced mortality in ISIS-2. Lancet 1:502

    Google Scholar 

  5. van Domburg RT, Sonnenschein K, Nieuwlaat R, Kamp O, Storm CJ, Bax JJ, Simoons ML (2005) Sustained benefit 20 years after reperfusion therapy in acute myocardial infarction. J Am Coll Cardiol 46:15–20

    PubMed  Google Scholar 

  6. Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion – a target for cardioprotection. Cardiovasc Res 61:372–385

    PubMed  CAS  Google Scholar 

  7. Piper HM, Garcia-Dorado D, Ovize M (1998) A fresh look at reperfusion injury. Cardiovasc Res 38:291–300

    PubMed  CAS  Google Scholar 

  8. Miyazaki S, Fujiwara H, Onodera T, Kihara Y, Matsuda M, Wu D, Nakamura Y, Kumada T, Sasayama S, Kawai C, Hamashima Y (1987) Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart. Circulation 75:1074–1082

    PubMed  CAS  Google Scholar 

  9. Barrabes JA, Garcia-Dorado D, Ruiz-Meana M, Piper HM, Solares J, Gonzalez MA, Oliveras J, Herrejon MP, Soler SJ (1996) Myocardial segment shrinkage during coronary reperfusion in situ. Relation to hypercontracture and myocardial necrosis. Pflugers Arch 431:519–526

    PubMed  CAS  Google Scholar 

  10. Garcia-Dorado D, Inserte J, Ruiz-Meana M, Gonzalez MA, Solares J, Julia M, Barrabes JA, Soler-Soler J (1997) Gap junction uncoupler heptanol prevents cell-to-cell progression of hypercontracture and limits necrosis during myocardial reperfusion. Circulation 96:3579–3586

    PubMed  CAS  Google Scholar 

  11. Inserte J, Garcia-Dorado D, Ruiz-Meana M, Padilla F, Barrabes JA, Pina P, Agullo L, Piper HM, Soler-Soler J (2002) Effect of inhibition of Na(+)/Ca(2+) exchanger at the time of myocardial reperfusion on hypercontracture and cell death. Cardiovasc Res 55:739–748

    PubMed  CAS  Google Scholar 

  12. Garcia-Dorado D, Theroux P, Duran JM, Solares J, Alonso J, Sanz E, Munoz R, Elizaga J, Botas J, Fernandez-Aviles F (1992) Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion. Circulation 85:1160–1174

    PubMed  CAS  Google Scholar 

  13. Inserte J, Garcia-Dorado D, Hernando V, Soler-Soler J (2005) Calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia. Circ Res 97:465–473

    PubMed  CAS  Google Scholar 

  14. Sebbag L, Verbinski SG, Reimer KA, Jennings RB (2003) Protection of ischemic myocardium in dogs using intracoronary 2,3-butanedione monoxime (BDM). J Mol Cell Cardiol 35:165–176

    PubMed  CAS  Google Scholar 

  15. Schlack W, Uebing A, Schafer M, Bier F, Schafer S, Piper HM, Thamer V (1994) Regional contractile blockade at the onset of reperfusion reduces infarct size in the dog heart. Pflugers Arch 428:134–141

    PubMed  CAS  Google Scholar 

  16. Siegmund B, Klietz T, Schwartz P, Piper HM (1991) Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated cardiomyocytes. Am J Physiol 260:H426–H435

    PubMed  CAS  Google Scholar 

  17. Schafer C, Ladilov Y, Inserte J, Schafer M, Haffner S, Garcia-Dorado D, Piper HM (2001) Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury. Cardiovasc Res 51:241–250

    PubMed  CAS  Google Scholar 

  18. Ladilov Y, Efe O, Schafer C, Rother B, Kasseckert S, Abdallah Y, Meuter K, Dieter SK, Piper HM (2003) Reoxygenation-induced rigor-type contracture. J Mol Cell Cardiol 35:1481–1490

    PubMed  CAS  Google Scholar 

  19. Ventura-Clapier R, Veksler V (1994) Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness. Circ Res 74:920–929

    PubMed  CAS  Google Scholar 

  20. Nichols CG, Lederer WJ (1990) The role of ATP in energy-deprivation contractures in unloaded rat ventricular myocytes. Can J Physiol Pharmacol 68:183–194

    PubMed  CAS  Google Scholar 

  21. Bennett V, Gilligan DM (1993) The spectrin-based membrane skeleton and micron-scale organization of the plasma membrane. Annu Rev Cell Biol 9:27–66

    PubMed  CAS  Google Scholar 

  22. Inserte J, Garcia-Dorado D, Ruiz-Meana M, Agullo L, Pina P, Soler-Soler J (2004) Ischemic preconditioning attenuates calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism. Cardiovasc Res 64:105–114

    PubMed  CAS  Google Scholar 

  23. Rodriguez-Sinovas A, Garcia-Dorado D, Ruiz-Meana M, Soler-Soler J (2004) Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium. J Physiol 559:245–257

    PubMed  CAS  Google Scholar 

  24. Garcia-Dorado D, Theroux P, Desco M, Solares J, Elizaga J, Fernandez-Aviles F, Alonso J, Soriano J (1989) Cell-to-cell interaction: a mechanism to explain wave-front progression of myocardial necrosis. Am J Physiol 256:H1266–H1273

    PubMed  CAS  Google Scholar 

  25. Frantseva MV, Kokarovtseva L, Perez Velazquez JL (2002) Ischemia-induced brain damage depends on specific gap-junctional coupling. J Cereb Blood Flow Metab 22:453–462

    PubMed  Google Scholar 

  26. Lin JH, Weigel H, Cotrina ML, Liu S, Bueno E, Hansen AJ, Hansen TW, Goldman S, Nedergaard M (1998) Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci 1:494–500

    PubMed  CAS  Google Scholar 

  27. Rami A, Volkmann T, Winckler J (2001) Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia. Exp Neurol 170:297–304

    PubMed  CAS  Google Scholar 

  28. Rawanduzy A, Hansen A, Hansen TW, Nedergaard M (1997) Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke. J Neurosurg 87:916–920

    Article  PubMed  CAS  Google Scholar 

  29. Garcia-Dorado D, Rodriguez-Sinovas A, Ruiz-Meana M (2004) Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion. Cardiovasc Res 61:386–401

    PubMed  CAS  Google Scholar 

  30. Garcia-Dorado D, Rodriguez-Sinovas A, Ruiz-Meana M, Inserte J, Agullo L, Cabestrero A (2006) The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion. Cardiovasc Res 70:274–285

    PubMed  CAS  Google Scholar 

  31. Schwanke U, Konietzka I, Duschin A, Li X, Schulz R, Heusch G (2002) No ischemic preconditioning in heterozygous connexin43-deficient mice. Am J Physiol Heart Circ Physiol 283:H1740–H1742

    PubMed  CAS  Google Scholar 

  32. Li X, Heinzel FR, Boengler K, Schulz R, Heusch G (2004) Role of connexin 43 in ischemic preconditioning does not involve intercellular communication through gap junctions. J Mol Cell Cardiol 36:161–163

    PubMed  CAS  Google Scholar 

  33. Boengler K, Dodoni G, Rodriguez-Sinovas A, Cabestrero A, Ruiz-Meana M, Gres P, Konietzka I, Lopez-Iglesias C, Garcia-Dorado D, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244

    PubMed  CAS  Google Scholar 

  34. Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, Konietzka I, Miro E, Totzeck A, Heusch G, Schulz R, Garcia-Dorado D (2006) Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99:93–101

    PubMed  CAS  Google Scholar 

  35. Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, Garcia-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586

    PubMed  CAS  Google Scholar 

  36. Bernardi P, Krauskopf A, Basso E, Petronilli V, Blachly-Dyson E, Di Lisa F, Forte MA (2006) The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 273:2077–2099

    PubMed  CAS  Google Scholar 

  37. Piper HM, Abdallah Y, Schafer C (2004) The first minutes of reperfusion: a window of opportunity for cardioprotection. Cardiovasc Res 61:365–371

    PubMed  CAS  Google Scholar 

  38. Griffiths EJ, Halestrap AP (1995) Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307:93–98

    PubMed  CAS  Google Scholar 

  39. Di Lisa F, Menabo R, Canton M, Barile M, Bernardi P (2001) Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart. J Biol Chem 276:2571–2575

    PubMed  CAS  Google Scholar 

  40. Argaud L, Gateau-Roesch O, Chalabreysse L, Gomez L, Loufouat J, Thivolet-Bejui F, Robert D, Ovize M (2004) Preconditioning delays Ca2+-induced mitochondrial permeability transition. Cardiovasc Res 61:115–122

    PubMed  CAS  Google Scholar 

  41. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M (2005) Postconditioning inhibits mitochondrial permeability transition. Circulation 111:194–197

    PubMed  CAS  Google Scholar 

  42. Piper HM, Kasseckert S, Abdallah Y (2006) The sarcoplasmic reticulum as the primary target of reperfusion protection. Cardiovasc Res 70:170–173

    PubMed  CAS  Google Scholar 

  43. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658–662

    PubMed  CAS  Google Scholar 

  44. Schinzel AC, Takeuchi O, Huang Z, Fisher JK, Zhou Z, Rubens J, Hetz C, Danial NN, Moskowitz MA, Korsmeyer SJ (2005) Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci USA 102:12005–12010

    PubMed  CAS  Google Scholar 

  45. Becker LB (2004) New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res 61:461–470

    PubMed  CAS  Google Scholar 

  46. Schulz R, Cohen MV, Behrends M, Downey JM, Heusch G (2001) Signal transduction of ischemic preconditioning. Cardiovasc Res 52:181–198

    PubMed  CAS  Google Scholar 

  47. Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151

    PubMed  CAS  Google Scholar 

  48. Zaugg M, Schaub MC (2003) Signaling and cellular mechanisms in cardiac protection by ischemic and pharmacological preconditioning. J Muscle Res Cell Motil 24:219–249

    PubMed  CAS  Google Scholar 

  49. Schwartz LM, Lagranha CJ (2006) Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs. Am J Physiol Heart Circ Physiol 290:H1011–H1018

    PubMed  CAS  Google Scholar 

  50. Tang XL, Sato H, Tiwari S, Dawn B, Bi Q, Li Q, Shirk G, Bolli R (2006) Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min. Am J Physiol Heart Circ Physiol 291:H2308–H2317

    PubMed  CAS  Google Scholar 

  51. Crisostomo PR, Wang M, Wairiuko GM, Terrell AM, Meldrum DR (2006) Postconditioning in females depends on injury severity. J Surg Res 134:342–347

    PubMed  Google Scholar 

  52. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85

    PubMed  CAS  Google Scholar 

  53. Heusch G (2004) Postconditioning: old wine in a new bottle? J Am Coll Cardiol 44:1111–1112

    PubMed  Google Scholar 

  54. Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75

    PubMed  CAS  Google Scholar 

  55. Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV (2006) Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res 70:308–314

    PubMed  CAS  Google Scholar 

  56. Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM (2004) Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 95:230–232

    PubMed  CAS  Google Scholar 

  57. Yang XM, Philipp S, Downey JM, Cohen MV (2005) Postconditioning’s protection is not dependent on circulatin blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation. Basic Res Cardiol 100:57–63

    PubMed  CAS  Google Scholar 

  58. Zhu M, Feng J, Lucchinetti E, Fischer G, Xu L, Pedrazzini T, Schaub MC, Zaugg M (2006) Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res 72:152–162

    PubMed  CAS  Google Scholar 

  59. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L’Huillier I, Aupetit JF, Bonnefoy E, Finet G, Andre-Fouet X, Ovize M (2005) Postconditioning the human heart. Circulation 112:2143–2148

    PubMed  Google Scholar 

  60. Rupprecht HJ, vom DJ, Terres W, Seyfarth KM, Richardt G, Schultheibeta HP, Buerke M, Sheehan FH, Drexler H (2000) Cardioprotective effects of the Na(+)/H(+) exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA. Circulation 101:2902–2908

    PubMed  CAS  Google Scholar 

  61. Tardif JC, Mercier LA, Theroux P (2004) Effect of inhibition of the Na+/H+ exchanger with cariporide on left ventricular function in acute coronary syndromes: results from the echocardiographic substudy of the GUARDIAN trial. Can J Cardiol 20:317–322

    PubMed  CAS  Google Scholar 

  62. Theroux P, Chaitman BR, Danchin N, Erhardt L, Meinertz T, Schroeder JS, Tognoni G, White HD, Willerson JT, Jessel A (2000) Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard during ischemia against necrosis (GUARDIAN) Investigators. Circulation 102:3032–3038

    PubMed  CAS  Google Scholar 

  63. Tzivoni D, Baer F, Fernandez Ortiz A, Heyndrickx G, Brachmann J, Reiber H, Krucoff M, Tatsuno J, Davies M, Hibberd M (2004) Reduction of infarct size and improved left ventricular function with intravenous calderet (MCC-135) and primary percutaneous coronary intervention for ST-elevation myocardial infarction. J Am Coll Cardiol; Abstracts from the American College of Cardiology 2004, 53rd Annual Scientific Session:- Abstract presentation No 25–27

  64. Zeymer U, Suryapranata H, Monassier JP, Opolski G, Davies J, Rasmanis G, Linssen G, Tebbe U, Schroder R, Tiemann R, Machnig T, Neuhaus KL (2001) 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 cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial. J Am Coll Cardiol 38:1644–1650

    PubMed  CAS  Google Scholar 

  65. Gasparetto C, Malinverno A, Culacciati D, Gritti D, Prosperini PG, Specchia G, Ricevuti G (2005) Antioxidant vitamins reduce oxidative stress and ventricular remodeling in patients with acute myocardial infarction. Int J Immunopathol Pharmacol 18:487–496

    PubMed  CAS  Google Scholar 

  66. Tsujita K, Shimomura H, Kawano H, Hokamaki J, Fukuda M, Yamashita T, Hida S, Nakamura Y, Nagayoshi Y, Sakamoto T, Yoshimura M, Arai H, Ogawa H (2004) Effects of edaravone on reperfusion injury in patients with acute myocardial infarction. Am J Cardiol 94:481–484

    PubMed  CAS  Google Scholar 

  67. Flaherty JT, Pitt B, Gruber JW, Heuser RR, Rothbaum DA, Burwell LR, George BS, Kereiakes DJ, Deitchman D, Gustafson N (1994) Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation 89:1982–1991

    PubMed  CAS  Google Scholar 

  68. Quintana M, Hjemdahl P, Sollevi A, Kahan T, Edner M, Rehnqvist N, Swahn E, Kjerr AC, Nasman P (2003) Left ventricular function and cardiovascular events following adjuvant therapy with adenosine in acute myocardial infarction treated with thrombolysis, results of the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study. Eur J Clin Pharmacol 59:1–9

    PubMed  CAS  Google Scholar 

  69. Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW (2005) 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 45:1775–1780

    PubMed  CAS  Google Scholar 

  70. Kopecky SL, Aviles RJ, Bell MR, Lobl JK, Tipping D, Frommell G, Ramsey K, Holland AE, Midei M, Jain A, Kellett M, Gibbons RJ (2003) A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study. Am Heart J 146:146–152

    PubMed  CAS  Google Scholar 

  71. Marzilli M, Orsini E, Marraccini P, Testa R (2000) Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 101:2154–2159

    PubMed  CAS  Google Scholar 

  72. Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, Eisenberg PR, Bolli R, Casas AC, Molina-Viamonte V, Orlandi C, Blevins R, Gibbons RJ, Califf RM, Granger CB (1999) 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 34:1711–1720

    PubMed  CAS  Google Scholar 

  73. Briguori C, Colombo A, Airoldi F, Violante A, Focaccio A, Balestrieri P, Paolo EP, Golia B, Lepore S, Riviezzo G, Scarpato P, Librera M, Bonizzoni E, Ricciardelli B (2004) Statin administration before percutaneous coronary intervention: impact on periprocedural myocardial infarction. Eur Heart J 25:1822–1828

    PubMed  CAS  Google Scholar 

  74. Chyrchel M, Rakowski T, Rzeszutko L, Legutko J, Dziewierz A, Dubiel JS, Dudek D (2006) Effects of high-dose statin administered prior to coronary angioplasty on the incidence of cardiac events in patients with acute coronary syndrome. Kardiol Pol 64:1357–1362

    PubMed  Google Scholar 

  75. Collard CD, Body SC, Shernan SK, Wang S, Mangano DT (2006) Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 132:392–400

    PubMed  CAS  Google Scholar 

  76. Ishii H, Ichimiya S, Kanashiro M, Aoyama T, Ogawa Y, Murakami R, Amano T, Naruse K, Matsubara T, Murohara T (2006) Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention. Clin Ther 28:1812–1819

    PubMed  CAS  Google Scholar 

  77. Mulukutla SR, Marroquin OC, Smith C, Varghese R, Anderson WD, Lee JS, Cohen HA, Counihan PJ, Lee AB, Gulati V, McNamara D (2004) Effect of statin therapy prior to elective percutaneous coronary intervention on frequency of periprocedural myocardial injury. Am J Cardiol 94:1363–1366

    PubMed  CAS  Google Scholar 

  78. Penning-van Beest FJ, Termorshuizen F, Goettsch WG, Klungel OH, Kastelein JJ, Herings RM (2006) Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study. Eur Heart J 28:154–159

    PubMed  Google Scholar 

  79. Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G (2004) Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation 110:674–678

    PubMed  CAS  Google Scholar 

  80. Hong YJ, Jeong MH, Hwang SH, Yun NS, Lee SR, Hong SN, Kim KH, Park HW, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC (2006) Effect of combination therapy with simvastatin and carvedilol in patients with left ventricular dysfunction complicated with acute myocardial infarction who underwent percutaneous coronary intervention. Circ J 70:1269–1274

    PubMed  CAS  Google Scholar 

  81. Pan W, Pintar T, Anton J, Lee VV, Vaughn WK, Collard CD (2004) Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery. Circulation 110:II45–II49

    PubMed  Google Scholar 

  82. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T (2001) Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 285:1711–1718

    PubMed  CAS  Google Scholar 

  83. Sakamoto T, Kojima S, Ogawa H, Shimomura H, Kimura K, Ogata Y, Sakaino N, Kitagawa A (2006) Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese. Am J Cardiol 97:1165–1171

    PubMed  CAS  Google Scholar 

  84. Fonarow GC, Wright RS, Spencer FA, Fredrick PD, Dong W, Every N, French WJ (2005) Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol 96:611–616

    PubMed  CAS  Google Scholar 

  85. Herrmann J, Lerman A, Baumgart D, Volbracht L, Schulz R, von Birgelen C, Haude M, Heusch G, Erbel R (2002) Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction. Circulation 106:2180–2183

    PubMed  CAS  Google Scholar 

  86. Amit G, Cafri C, Yaroslavtsev S, Fuchs S, Paltiel O, Abu-Ful A, Weinstein JM, Wolak A, Ilia R, Zahger D (2006) Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial. Am Heart J 152:887.e9–887.e14

    Google Scholar 

  87. Kiziltepe U, Tunctan B, Eyileten ZB, Sirlak M, Arikbuku M, Tasoz R, Uysalel A, Ozyurda U (2004) Efficiency of l-arginine enriched cardioplegia and non-cardioplegic reperfusion in ischemic hearts. Int J Cardiol 97:93–100

    PubMed  Google Scholar 

  88. Ikeda N, Yasu T, Kubo N, Hashimoto S, Tsuruya Y, Fujii M, Kawakami M, Saito M (2004) Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction. Heart 90:181–185

    PubMed  CAS  Google Scholar 

  89. ISIS-4 (1995) A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 345:669–685

    Google Scholar 

  90. Kitakaze M, Asakura M, Shintani Y, Asanuma H, Seguchi O, Myoishi M, Minamino T, Kim J, J-WIND investigators (2006) Large-scale trial using natriuretic peptide or nicorandil as an adjunct to percutaneous coronary intervention for ST-segment elevation acute myocardial infarction. Circulation 114:2425–2426

    Google Scholar 

  91. Ono H, Osanai T, Ishizaka H, Hanada H, Kamada T, Onodera H, Fujita N, Sasaki S, Matsunaga T, Okumura K (2004) Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation. Am Heart J 148:E15

    PubMed  Google Scholar 

  92. Toyama T, Seki R, Hoshizaki H, Kawaguchi R, Isobe N, Adachi H, Oshima S, Taniguchi K, Kasama S (2006) Nicorandil administration shows cardioprotective effects in patients with poor TIMI and collateral flow as well as good flow after AMI. Ann Nucl Med 20:277–285

    Article  PubMed  CAS  Google Scholar 

  93. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M (2005) Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction. Eur J Nucl Med Mol Imaging 32:322–328

    PubMed  CAS  Google Scholar 

  94. Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K, Minamino T (1999) Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol 33:654–660

    PubMed  CAS  Google Scholar 

  95. Sakata Y, Kodama K, Komamura K, Lim YJ, Ishikura F, Hirayama A, Kitakaze M, Masuyama T, Hori M (1997) Salutary effect of adjunctive intracoronary nicorandil administration on restoration of myocardial blood flow and functional improvement in patients with acute myocardial infarction. Am Heart J 133:616–621

    PubMed  CAS  Google Scholar 

  96. Ceremuzynski L, Budaj A, Czepiel A, Burzykowski T, Achremczyk P, Smielak-Korombel W, Maciejewicz J, Dziubinska J, Nartowicz E, Kawka-Urbanek T, Piotrowski W, Hanzlik J, Cieslinski A, Kawecka-Jaszcz K, Gessek J, Wrabec K (1999) Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter Pol-GIK trial. Cardiovasc Drugs Ther 13:191–200

    PubMed  CAS  Google Scholar 

  97. Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalan R, Isea JE, Romero G (1998) Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circulation 98:2227–2234

    PubMed  CAS  Google Scholar 

  98. Mehta SR, Yusuf S, Diaz R, Zhu J, Pais P, Xavier D, Paolasso E, Ahmed R, Xie C, Kazmi K, Tai J, Orlandini A, Pogue J, Liu L (2005) Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. JAMA 293:437–446

    PubMed  Google Scholar 

  99. Pache J, Kastrati A, Mehilli J, Bollwein H, Ndrepepa G, Schuhlen H, Martinoff S, Seyfarth M, Nekolla S, Dirschinger J, Schwaiger M, Schomig A (2004) A randomized evaluation of the effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J 148:e3

    PubMed  Google Scholar 

  100. Timmer JR, van der Horst I, Ottervanger JP, De Luca G, van’t Hof AW, Bilo HJ, Zijlstra F (2004) Glucose-insulin-potassium infusion as adjunctive therapy in myocardial infarction: current evidence and potential mechanisms. Ital Heart J 5:727–731

    PubMed  Google Scholar 

  101. Timmer JR, Svilaas T, Ottervanger JP, Henriques JP, Dambrink JH, van den Broek SA, van der Horst I, Zijlstra F (2006) Glucose-insulin-potassium infusion in patients with acute myocardial infarction without signs of heart failure: the Glucose-Insulin-Potassium Study (GIPS)-II. J Am Coll Cardiol 47:1730–1731

    PubMed  CAS  Google Scholar 

  102. Zhang L, Zhang L, Li YH, Zhang HY, Chen ML, Gao MM, Hu AH, Yang HS, Yang HS (2005) High-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarction. Eur J Clin Invest 35:164–170

    PubMed  CAS  Google Scholar 

  103. van der Horst I, Zijlstra F, van’t Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, Hoorntje JC, Dambrink JH, Gans RO, Bilo HJ (2003) Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. J Am Coll Cardiol 42:784–791

    PubMed  Google Scholar 

  104. Lipsic E, van der Meer P, Voors AA, Westenbrink BD, van den Heuvel AF, de Boer HC, van Zonneveld AJ, Schoemaker RG, van Gilst WH, Zijlstra F, van Veldhuisen DJ (2006) A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 20:135–141

    PubMed  CAS  Google Scholar 

  105. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kaski JC, Reiter RJ, Jimenez-Sosa A (2006) A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale. Contemp Clin Trials doi:10.1016/j.cct.2006.10.007

  106. Hayashi M, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Tsutsui T, Horie H, Ohnishi M, Kinoshita M (2001) Intravenous atrial natriuretic peptide prevents left ventricular remodeling in patients with first anterior acute myocardial infarction. J Am Coll Cardiol 37:1820–1826

    PubMed  CAS  Google Scholar 

  107. Kuga H, Ogawa K, Oida A, Taguchi I, Nakatsugawa M, Hoshi T, Sugimura H, Abe S, Kaneko N (2003) Administration of atrial natriuretic peptide attenuates reperfusion phenomena and preserves left ventricular regional wall motion after direct coronary angioplasty for acute myocardial infarction. Circ J 67:443–448

    PubMed  CAS  Google Scholar 

  108. Asakura M, Jiyoong K, Minamino T, Shintani Y, Asanuma H, Kitakaze M (2004) Rationale and design of a large-scale trial using atrial natriuretic peptide (ANP) as an adjunct to percutaneous coronary intervention for ST-segment elevation acute myocardial infarction: Japan-working groups of acute myocardial infarction for the reduction of Necrotic Damage by ANP (J-WIND-ANP). Circ J 68:95–100

    PubMed  CAS  Google Scholar 

  109. Kurz T, Schafer U, Dendorfer A, Hartmann F, Raasch W, Tolg R, Remppis A, Giannitsis E, Dominiak P, Katus HA, Richardt G (2001) Effects of intracoronary low-dose enalaprilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction. Am J Cardiol 88:1351–1357

    PubMed  CAS  Google Scholar 

  110. Schaefer U, Kurz T, Bonnemeier H, Dendorfer A, Hartmann F, Schunkert H, Richardt G (2007) Intracoronary enalaprilat during angioplasty for acute myocardial infarction: alleviation of postischaemic neurohumoral and inflammatory stress? J Intern Med 261:188–200

    PubMed  CAS  Google Scholar 

  111. Walter T, Helber U, Bail D, Heller W, Hoffmeister HM (2002) Influence of ACE inhibition on myocardial damage, the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery. Thorac Cardiovasc Surg 50:150–154

    PubMed  CAS  Google Scholar 

  112. The EMIP-FR Group (2000) Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. European Myocardial Infarction Project – Free Radicals. Eur Heart J 21:1537–1546

  113. Rodriguez-Sinovas A, Garcia-Dorado D, Padilla F, Inserte J, Barrabes JA, Ruiz-Meana M, Agullo L, Soler-Soler J (2003) Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia. Cardiovasc Res 58:109–117

    PubMed  CAS  Google Scholar 

  114. Garcia-Dorado D, Gonzalez MA, Barrabes JA, Ruiz-Meana M, Solares J, Lidon RM, Blanco J, Puigfel Y, Piper HM, Soler-Soler J (1997) Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H+ exchange. Cardiovasc Res 35:80–89

    PubMed  CAS  Google Scholar 

  115. Klein HH, Pich S, Bohle RM, Lindert-Heimberg S, Nebendahl K (2000) Na(+)/H(+) exchange inhibitor cariporide attenuates cell injury predominantly during ischemia and not at onset of reperfusion in porcine hearts with low residual blood flow. Circulation 102:1977–1982

    PubMed  CAS  Google Scholar 

  116. van der Horst I, Zijlstra F, van’t Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, Hoorntje JC, Dambrink JH, Gans RO, Bilo HJ (2003) Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. J Am Coll Cardiol 42:784–791

    PubMed  Google Scholar 

  117. Schneider A, Ad N, Izhar U, Khaliulin I, Borman JB, Schwalb H (2003) Protection of myocardium by cyclosporin A and insulin: in vitro simulated ischemia study in human myocardium. Ann Thorac Surg 76:1240–1245

    PubMed  Google Scholar 

  118. Imahashi K, Pott C, Goldhaber JI, Steenbergen C, Philipson KD, Murphy E (2005) Cardiac-specific ablation of the Na+-Ca2+ exchanger confers protection against ischemia/reperfusion injury. Circ Res 97:916–921

    PubMed  CAS  Google Scholar 

  119. Forman MB, Stone GW, Jackson EK (2006) Role of adenosine as adjunctive therapy in acute myocardial infarction. Cardiovasc Drug Rev 24:116–147

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Partially supported by the Spanish Ministry of Health (RECAVA). Antonio Rodríguez-Sinovas is a recipient of a contract from the Generalitat de Catalunya (Programa d’estabilització d’investigadors, Departament de Salut, Direcció d’Estratègia i Coordinació).

Author information

Authors and Affiliations

  1. Laboratorio de Cardiología Experimental, Servicio de Cardiología, Hospital Universitario Vall d’Hebron, Pg. Vall d’Hebron 119, Barcelona, 08035, Spain

    Antonio Rodríguez-Sinovas & David Garcia-Dorado

  2. Institute of Physiology, Justus Liebig University, Aulweg 129, 35392, Giessen, Germany

    Yaser Abdallah & Hans Michael Piper

Authors
  1. Antonio Rodríguez-Sinovas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yaser Abdallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Michael Piper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Garcia-Dorado
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hans Michael Piper or David Garcia-Dorado.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rodríguez-Sinovas, A., Abdallah, Y., Piper, H.M. et al. Reperfusion injury as a therapeutic challenge in patients with acute myocardial infarction. Heart Fail Rev 12, 207–216 (2007). https://doi.org/10.1007/s10741-007-9039-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-007-9039-9

Keywords

Search

Navigation