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Cardiovascular Drugs and Therapy

, Volume 28, Issue 2, pp 173–181 | Cite as

Reduced Oxidative Stress in STEMI Patients Treated by Primary Percutaneous Coronary Intervention and with Antioxidant Therapy: A Systematic Review

  • Sarah EkeløfEmail author
  • Svend Eggert Jensen
  • Jacob Rosenberg
  • Ismail Gögenur
REVIEW ARTICLE

Abstract

Purpose

Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage—a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI.

Methods

We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine.

Results

Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown.

Conclusions

Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.

Keywords

Ischemia-reperfusion injury Antioxidant therapy Acute myocardial infarction Oxidative stress 

Notes

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Hausenloy DJ, Yellon DM. Time to take myocardial reperfusion injury seriously. N Engl J Med. 2008;359:518–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357:1121–35.PubMedCrossRefGoogle Scholar
  3. 3.
    Qin C, Yap S, Woodman OL. Antioxidants in the prevention of myocardial ischemia/reperfusion injury. Expert Rev Clin Pharmacol. 2009;2:673–95.PubMedCrossRefGoogle Scholar
  4. 4.
    Stebbins A, Mehta RH, Armstrong PW, et al. A model for predicting mortality in acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: results from the Assessment of Pexelizumab in Acute Myocardial Infarction Trial. Circ Cardiovasc Interv. 2010;3:414–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Tullio F, Angotti C, Perrelli M-G, Penna C, Pagliaro P. Redox balance and cardioprotection. Basic Res Cardiol. 2012;108:392.CrossRefGoogle Scholar
  6. 6.
    Perrelli MG, Pagliaro P, Penna C. Ischemia/reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. World J Cardiol. 2011;3:186–200.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Berg K, Jynge P, Bjerve K, Skarra S, Basu S, Wiseth R. Oxidative stress and inflammatory response during and following coronary interventions for acute myocardial infarction. Free Radic Res. 2005;39:629–36.PubMedCrossRefGoogle Scholar
  8. 8.
    Kijima Y, Hashimura K, Matsu-ura Y, et al. Transcardiac 8-iso-prostaglandin F(2 alpha) generation from acute myocardial infarction heart: insight into abrupt reperfusion and oxidant stress. Prostaglandins Leukot Essent Fat Acids. 2001;64:161–6.CrossRefGoogle Scholar
  9. 9.
    Sugamura K, Keaney Jr JF. Reactive oxygen species in cardiovascular disease. Free Radic Biol Med. 2011;51:978–92.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Kutala VK, Khan M, Angelos MG, Kuppusamy P. Role of oxygen in postischemic myocardial injury. Antioxid Redox Signal. 2007;9:1193–206.PubMedCrossRefGoogle Scholar
  11. 11.
    Himmetoglu S, Dincer Y, Bozcali E, Ali Vural V, Akcay T. Oxidative DNA damage and antioxidant defense after reperfusion in acute myocardial infarction. J Investig Med. 2009;57:595–9.PubMedGoogle Scholar
  12. 12.
    Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151:W65–94.PubMedCrossRefGoogle Scholar
  13. 13.
    Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Tsujita K, Shimomura H, Kaikita K, et al. Long-term efficacy of edaravone in patients with acute myocardial infarction. Circ J. 2006;70:832–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Guan W, Osanai T, Kamada T, et al. Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction. J Cardiovasc Pharmacol. 2003;41:699–705.PubMedCrossRefGoogle Scholar
  16. 16.
    Guan W, Osanai T, Kamada T, Ishizaka H, Hanada H, Okumura K. Time course of free radical production after primary coronary angioplasty for acute myocardial infarction and the effect of vitamin C. Jpn Circ J. 1999;63:924–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Ono H, Osanai T, Ishizaka H, et al. 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. 2004;148:E15.PubMedCrossRefGoogle Scholar
  18. 18.
    Thiele H, Hildebrand L, Schirdewahn C, et al. Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Protective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am Coll Cardiol. 2010;55:2201–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Díaz-Araya G, Nettle D, Castro P, et al. Oxidative stress after reperfusion with primary coronary angioplasty: lack of effect of glucose-insulin-potassium infusion. Crit Care Med. 2002;30:417–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Chan W, Taylor AJ, Ellims AH, et al. Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction. Circ Cardiovasc Interv. 2012;5:270–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen M, Li H, Wang Y. Protection by atorvastatin pretreatment in patients undergoing primary percutaneous coronary intervention is associated with the lower levels of oxygen free radicals. J Cardiovasc Pharmacol. 2013;62:320–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Carreira RS, Monteiro P, Kowaltowski AJ, Goncalves LM, Providência LA. Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion. J Bioenerg Biomembr. 2008;40:95–102.PubMedCrossRefGoogle Scholar
  23. 23.
    Pieper GM, Gross GJ. Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. Cardiovasc Drugs Ther. 1992;6:225–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006;354:2773–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Demircan S, Yazici M, Diraman E, et al. The effect of glucose-insulin-potassium treatment on myocardial oxidative stress in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Coron Artery Dis. 2008;19:99–104.PubMedCrossRefGoogle Scholar
  26. 26.
    Rosenson RS. Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis. 2004;173:1–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Wassmann S, Laufs U, Müller K, et al. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2002;22:300–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Reilly MP, Delanty N, Roy L, et al. Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary angioplasty: evidence for oxidant stress during coronary reperfusion in humans. Circulation. 1997;96:3314–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Molyneux CA, Glyn MC, Ward BJ. Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins. Microvasc Res. 2002;64:265–77.PubMedCrossRefGoogle Scholar
  30. 30.
    Kinugasa Y, Ogino K, Furuse Y, et al. Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts. Circ J. 2003;67:781–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Williams RE, Zweier JL, Flaherty JT. Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts. Circulation. 1991;83:1006–14.PubMedCrossRefGoogle Scholar
  32. 32.
    Han B, Zhang X, Zhang Q, et al. Protective effects of salvianolate on microvascular flow in a porcine model of myocardial ischaemia and reperfusion. Arch Cardiovasc Dis. 2011;104:313–24.PubMedCrossRefGoogle Scholar
  33. 33.
    Onogi H, Minatoguchi S, Chen X-H, et al. Edaravone reduces myocardial infarct size and improves cardiac function and remodelling in rabbits. Clin Exp Pharmacol Physiol. 2006;33:1035–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Tsujita K, Shimomura H, Kawano H, et al. Effects of edaravone on reperfusion injury in patients with acute myocardial infarction. Am J Cardiol. 2004;94:481–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Nakamura Y, Yamada Y, Shimomura H, et al. Effect of edaravone on plasma monocyte chemoattractant protein-1 levels in patients with acute myocardial infarction. J Cardiol. 2009;54:416–24.PubMedCrossRefGoogle Scholar
  36. 36.
    Rentoukas E, Tsarouhas K, Tsitsimpikou C, Lazaros G, Deftereos S, Vavetsi S. The prognostic impact of allopurinol in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Int J Cardiol. 2010;145:257–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Patti G, Pasceri V, Colonna G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007;49:1272–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Sugimoto K, Ito H, Iwakura K, et al. Intravenous nicorandil in conjunction with coronary reperfusion therapy is associated with better clinical and functional outcomes in patients with acute myocardial infarction. Circ J. 2003;67:295–300.PubMedCrossRefGoogle Scholar
  39. 39.
    Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999;33:654–60.PubMedCrossRefGoogle Scholar
  40. 40.
    Kikuchi K, Takeshige N, Miura N, et al. Beyond free radical scavenging: beneficial effects of edaravone (Radicut) in various diseases (review). Exp Ther Med. 2012;3:3–8.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Wang A, Chen F, Xie Y, Guo Z, Yu Y. Protective mechanism of nicorandil on rat myocardial ischemia-reperfusion. J Cardiovasc Med (Hagerstown). 2012;13:511–5.CrossRefGoogle Scholar
  42. 42.
    Qian J, Keyes KT, Long B, Chen G, Ye Y. Impact of HMG-CoA reductase inhibition on oxidant-induced injury in human retinal pigment epithelium cells. J Cell Biochem. 2011;112:2480–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Pisarenko OI, Lakomkin VL, Studneva IM, et al. Allopurinol-enhanced postischemic recovery in the isolated rat heart involves repletion of high-energy phosphates. Biochem Med Metab Biol. 1994;51:16–26.PubMedCrossRefGoogle Scholar
  44. 44.
    Chambers DJ, Takahashi A, Humphrey SM, Harvey DM, Hearse DJ. Allopurinol-enhanced myocardial protection does not involve xanthine oxidase inhibition or purine salvage. Basic Res Cardiol. 1992;87:227–38.PubMedCrossRefGoogle Scholar
  45. 45.
    Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, et al. Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res. 2000;87:460–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Penna C, Mancardi D, Rastaldo R, Pagliaro P. Cardioprotection: a radical view Free radicals in pre and postconditioning. Biochim Biophys Acta. 2009;1787:781–93.PubMedCrossRefGoogle Scholar
  47. 47.
    Penna C, Rastaldo R, Mancardi D, et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol. 2006;101:180–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Cohen MV, Yang XM, Downey JM. Acidosis, oxygen, and interference with mitochondrial permeability transition pore formation in the early minutes of reperfusion are critical to postconditioning’s success. Basic Res Cardiol. 2008;103:464–71.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Hausenloy DJ, Ong SB, Yellon DM. The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol. 2009;104:189–202.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sarah Ekeløf
    • 1
    • 3
    Email author
  • Svend Eggert Jensen
    • 2
  • Jacob Rosenberg
    • 1
  • Ismail Gögenur
    • 1
  1. 1.Department of Surgery, Herlev HospitalUniversity of CopenhagenHerlevDenmark
  2. 2.Department of CardiologyAalborg University HospitalAalborgDenmark
  3. 3.Copenhagen SDenmark

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