Skip to main content
SpringerLink
Log in

Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center

  • Original Research Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but—to the best of our knowledge—few studies have assessed this.

Objectives

Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury.

Methods

We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC).

Results

The peak CK-MB level was comparable between the two groups (P = 0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG.

Conclusions

In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population.

ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir) registration number: IRCT201301048698N8.

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. Smith EJ, Mathur A, Rothman MT. Recent advances in primary percutaneous intervention for acute myocardial infarction. Heart (Br Card Soc). 2005;91:1533–6.

    Article  CAS  Google Scholar 

  2. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357:1121–35.

    Article  PubMed  CAS  Google Scholar 

  3. Mehta RH, Harjai KJ, Cox D, et al. Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention. J Am Coll Cardiol. 2003;42:1739–46.

    Article  PubMed  Google Scholar 

  4. De Luca G, van’t Hof AW, de Boer MJ, et al. Impaired myocardial perfusion is a major explanation of the poor outcome observed in patients undergoing primary angioplasty for ST-segment-elevation myocardial infarction and signs of heart failure. Circulation. 2004;109:958–61.

    Article  PubMed  Google Scholar 

  5. Baks T, van Geuns RJ, Biagini E, et al. Effects of primary angioplasty for acute myocardial infarction on early and late infarct size and left ventricular wall characteristics. J Am Coll Cardiol. 2006;47:40–4.

    Article  PubMed  Google Scholar 

  6. Okmen E, Kasikcioglu H, Sanli A, Uyarel H, Cam N. Correlations between cardiac troponin I, cardiac troponin T, and creatine phosphokinase MB elevation following successful percutaneous coronary intervention and prognostic value of each marker. J Invasive Cardiol. 2005;17:63–7.

    PubMed  Google Scholar 

  7. Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol. 2006;48:1–11.

    Article  PubMed  CAS  Google Scholar 

  8. Tzivoni D, Koukoui D, Guetta V, Novack L, Cowing G. Comparison of troponin T to creatine kinase and to radionuclide cardiac imaging infarct size in patients with ST-elevation myocardial infarction undergoing primary angioplasty. Am J Cardiol. 2008;101:753–7.

    Article  PubMed  CAS  Google Scholar 

  9. Salehi R, Alizadeh AA, Salehi A, Azarfarin R. The changes of cardiac troponin i and creatine kinase MB isoenzyme after percutaneous transluminal coronary angioplasty. J Cardiovasc Thorac Res. 2009;1:11–5.

    Google Scholar 

  10. Chia S, Senatore F, Raffel OC, Lee H, Wackers FJ, Jang IK. Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2008;1:415–23.

    Article  PubMed  Google Scholar 

  11. Feldman DN, Kim L, Rene AG, Minutello RM, Bergman G, Wong SC. Prognostic value of cardiac troponin-I or troponin-T elevation following nonemergent percutaneous coronary intervention: a meta-analysis. Catheter Cardiovasc Interv. 2011;77:1020–30.

    Article  PubMed  Google Scholar 

  12. Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123:92–100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Cusumano G, Romagnoli J, Liuzzo G, et al. N-Acetylcysteine and high-dose atorvastatin reduce oxidative stress in an ischemia-reperfusion model in the rat kidney. Transplant Proc (Elsevier). 2015;47:2757–62.

    Article  CAS  Google Scholar 

  14. Sochman J, Kolc J, Vrana M, Fabian J. Cardioprotective effects of N-acetylcysteine: the reduction in the extent of infarction and occurrence of reperfusion arrhythmias in the dog. Int J Cardiol. 1990;28:191–6.

    Article  PubMed  CAS  Google Scholar 

  15. Sochman J, Vrbska J, Musilova B, Rocek M. Infarct size limitation: acute N-acetylcysteine defense (ISLAND trial): preliminary analysis and report after the first 30 patients. Clin Cardiol. 1996;19:94–100.

    Article  PubMed  CAS  Google Scholar 

  16. Şentürk T, Çavun S, Avcı B, Yermezler A, Serdar Z, Savcı V. Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury. Atherosclerosis. 2014;237:760–6.

    Article  PubMed  CAS  Google Scholar 

  17. Prabhu A, Sujatha D, Kanagarajan N, Vijayalakshmi M, Ninan B. Effect of N-acetylcysteine in attenuating ischemic reperfusion injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Ann Vasc Surg. 2009;23:645–51.

    Article  PubMed  CAS  Google Scholar 

  18. Sochman J. N-Acetylcysteine somewhere between Scylla and Charybdis. J Am Coll Cardiol. 2010;56:1067 (author reply 1067–8).

    Article  PubMed  Google Scholar 

  19. Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569–619.

    Article  PubMed  CAS  Google Scholar 

  20. Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg. 2014;46:517–92.

    Article  PubMed  Google Scholar 

  21. Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93:879–88.

    Article  PubMed  CAS  Google Scholar 

  22. Gibson CM, Schomig A. Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion. Circulation. 2004;109:3096–105.

    Article  PubMed  Google Scholar 

  23. Henriques JP, Zijlstra F, van’t Hof AW, et al. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation. 2003;107:2115–9.

    Article  PubMed  Google Scholar 

  24. Jaffe R, Charron T, Puley G, Dick A, Strauss BH. Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation. 2008;117:3152–6.

    Article  PubMed  Google Scholar 

  25. Hillegass WB, Dean NA, Liao L, Rhinehart RG, Myers PR. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol. 2001;37:1335–43.

    Article  PubMed  CAS  Google Scholar 

  26. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53:31–47.

    Article  PubMed  CAS  Google Scholar 

  27. Haramaki N, Stewart DB, Aggarwal S, Ikeda H, Reznick AZ, Packer L. Networking antioxidants in the isolated rat heart are selectively depleted by ischemia-reperfusion. Free Radic Biol Med. 1998;25:329–39.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. Venardos KM, Kaye DM. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. Curr Med Chem. 2007;14:1539–49.

    Article  PubMed  CAS  Google Scholar 

  30. Serruys PW, De Feyter PJ, Benghozi R, Hugenholtz PG, Lesaffre E. The Lescol(R) Intervention Prevention Study (LIPS): a double-blind, placebo-controlled, randomized trial of the long-term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease. Int J Cardiovasc Interv. 2001;4:165–72.

    Article  Google Scholar 

  31. Ellis SG, Chew D, Chan A, Whitlow PL, Schneider JP, Topol EJ. Death following creatine kinase-MB elevation after coronary intervention: identification of an early risk period: importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy. Circulation. 2002;106:1205–10.

    Article  PubMed  CAS  Google Scholar 

  32. Chan AW, Bhatt DL, Chew DP, et al. Early and sustained survival benefit associated with statin therapy at the time of percutaneous coronary intervention. Circulation. 2002;105:691–6.

    Article  PubMed  CAS  Google Scholar 

  33. 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 (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am Coll Cardiol. 2010;55:2201–9.

    Article  PubMed  CAS  Google Scholar 

  34. Yesilbursa D, Serdar A, Senturk T, Serdar Z, Sag S, Cordan J. Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessels. 2006;21:33–7.

    Article  PubMed  Google Scholar 

  35. Arstall MAYJ, Stafford I, Betts WH, Horowitz JD. N-Acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Circulation. 1995;92:2855–62.

    Article  PubMed  CAS  Google Scholar 

  36. Pasupathy S, Tavella R, Grover S, Raman B, Procter NEK, Du YT, Mahadavan G, Stafford I, Heresztyn T, Holmes A, Zeitz C, Arstall M, Selvanayagam JB, Horowitz JD, Beltrame JF. Early use of N-acetylcysteine (NAC) with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction reduces myocardial infarct size (the NACIAM trial). Circulation. 2017;136(10):894–903. https://doi.org/10.1161/circulationaha.117.027575 (Epub ahead of print).

    Article  PubMed  CAS  Google Scholar 

  37. Andrews NP, Prasad A, Quyyumi AA. N-Acetylcysteine improves coronary and peripheral vascular function. J Am Coll Cardiol. 2001;37:117–23.

    Article  PubMed  CAS  Google Scholar 

  38. Meyer M, Bell SP, Chen Z, Nyotowidjojo I, Lachapelle RR, Christian TF, Gibson PC, Keating FF, Dauerman HL, LeWinter MM. High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction. J Thromb Thrombolysis. 2013;36(4):433–4.

    Article  PubMed  CAS  Google Scholar 

  39. Eshraghi A, Talasaz AH, Salamzadeh J, Salarifar M, Pourhosseini H, Nozari Y, Bahremand M, Jalali A, Boroumand MA. Evaluating the effect of intracoronary N-acetylcysteine on platelet activation markers after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction. Am J Ther. 2016;23(1):e44–51.

    Article  PubMed  Google Scholar 

  40. Horowitz JD, Henry CA, Syrjanen ML, Louis WJ, Fish RD, Smith TW, Antman EM. Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris. Circulation. 1988;77:787–94.

    Article  PubMed  CAS  Google Scholar 

  41. Beltrame JF, Zeitz CJ, Unger SA, Brennan RJ, Hunt A, Moran JL, Horowitz JD. Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema. J Card Fail. 1998;4:271–9.

    Article  PubMed  CAS  Google Scholar 

  42. Horowitz JD, Antman EM, Lorell BH, Barry WH, Smith TW. Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine. Circulation. 1983;68:1247–53.

    Article  PubMed  CAS  Google Scholar 

  43. Winniford MD, Kennedy PL, Wells PJ, Hillis LD. Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine. Circulation. 1986;73:138–42.

    Article  PubMed  CAS  Google Scholar 

  44. May DC, Popma JJ, Black WH, Schaefer S, Lee HR, Levine BD, Hillis LD. In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries. N Engl J Med. 1987;317:805–9.

    Article  PubMed  CAS  Google Scholar 

  45. Chirkov YY, Horowitz JD. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc Pharmacol. 1996;28:375–80.

    Article  PubMed  CAS  Google Scholar 

  46. Packer M, Lee WH, Kessler PD, Gottlieb SS, Medina N, Yushak M. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med. 1987;317:799–804.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge the considerable contribution made to this study by the staff of the Emergency Unit, Coronary Care Unit, Cardiac Catheterization Laboratory, and Laboratory of Tehran Heart Center.

Author information

Authors and Affiliations

  1. Tehran Heart Center, Tehran University of Medical Sciences, North Kargar Street, P.O. Box: 1411713138, Tehran, Iran

    Younes Nozari, Azita Hajhossein Talasaz, Mojtaba Salarifar, Hamidreza Pourhosseini, Arash Jalali & Seyedeh Hamideh Mortazavi

  2. Iran University of Medical Sciences, Tehran, Iran

    Azadeh Eshraghi

  3. Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mostafa Bahremand

  4. Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Jamshid Salamzadeh

Authors
  1. Younes Nozari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azadeh Eshraghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azita Hajhossein Talasaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mostafa Bahremand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jamshid Salamzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mojtaba Salarifar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamidreza Pourhosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arash Jalali
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Seyedeh Hamideh Mortazavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Azita Hajhossein Talasaz.

Ethics declarations

Funding

This study was supported by Tehran University of Medical Sciences.

Conflicts of interest

Younes Nozari, Azadeh Eshraghi, Azita Hajhossein Talasaz, Mostafa Bahremand, Jamshid Salamzadeh, Mojtaba Salarifar, Hamidreza Pourhosseini, Arash Jalali, and Seyedeh Hamideh Mortazavi declare that they have no potential conflicts of interest that might be relevant to this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nozari, Y., Eshraghi, A., Talasaz, A.H. et al. Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center. Am J Cardiovasc Drugs 18, 213–221 (2018). https://doi.org/10.1007/s40256-017-0258-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-017-0258-8

Search

Navigation