Pharmacological approaches to the prevention of myocardial ischemia-reperfusion injury in experimental study and clinical practice

Authors

  • S. M. Kozhukhov National Academy of Medical Science of Ukraine”, Kyiv,
  • O. M. Parkhomenko National Academy of Medical Science of Ukraine”, Kyiv,

DOI:

https://doi.org/10.14739/2310-1210.2019.4.173356

Keywords:

myocardial infarction, reperfusion, drug therapy

Abstract

 

Early reperfusion of the infarct related coronary artery is essential for the preservation of myocardial tissue and improve clinical outcome. The establishment of pharmacological and mechanical reperfusion treatment was a major improvement in the management of patients with myocardial infarction. However, this therapy is often complicated by reperfusion injury including ventricular arrhythmias, myocardial stunning and micro-vascular dysfunction, in addition to significant cardiomyocyte death. The most important factors which contribute to the reperfusion injury are an overproduction of reactive oxygen species, intracellular calcium overload and inflammatory cell infiltration. Some of these mechanisms may be interrelated. From considerations of their nature, an attractive hypothesis has been that some or several of these harmful effects may be counteracted by pharmacological interventions. This hypothesis has mainly been studied in the experimental setting.

Objective – in this review, various pharmacological interventions to treat myocardial reperfusion injury including the antioxidant flavonols, glucose – insulin – potassium therapy, adenosine, melatonin, phosphocreatine and cyclosporin A etc.

Conclusions. The processes involved in reperfusion injury might provide targets for improved outcomes after myocardial infarction but that aim has thus far not been met in the clinic. By studying new molecules in different experimental settings and protocols, insight has been gained about important factors for possible future clinical applications of drugs with cardioprotective properties.

 

References

  1. Dongworth, R., Campbell-Washburn, A., Cabrera-Fuentes, H., Bulluck, H., Roberts, T., Price, A.б et al. (2017). Quantifying the area-at-risk of myocardial infarction in-vivo using arterial spin labeling cardiac magnetic resonance. Scientific Reports, 7(1). 2271. doi: 10.1038/s41598-017-02544-z
  2. Rentrop, K., & Feit, F. (2015). Reperfusion therapy for acute myocardial infarction: Concepts and controversies from inception to acceptance. American Heart Journal, 170(5), 971–980. doi: 10.1016/j.ahj.2015.08.005
  3. Bouleti, C., Mewton, N., & Germain, S. (2015). The no-reflow phenomenon: State of the art. Archives of Cardiovascular Diseases, 108(12), 661–674. doi: 10.1016/j.acvd.2015.09.006
  4. Fröhlich, G., Meier, P., White, S., Yellon, D., & Hausenloy, D. (2013). Myocardial reperfusion injury: looking beyond primary PCI. European Heart Journal, 34(23), 1714–1722. doi: 10.1093/eurheartj/eht090
  5. van der Laan, A., Nahrendorf, M., & Piek, J. (2012). Healing and adverse remodelling after acute myocardial infarction: role of the cellular immune response. Heart, 98(18), 1384–1390. doi: 10.1136/heartjnl-2012-301623
  6. Gavrilenko, T., Parkhomenko, A., Ryzhkova, N., Kozhukhov, S., & Yakushko, L. (2013). Cytokine Profile of Mononuclear Cells in Patients with Acute Myocardial Infarction, Complicated by Heart Failure. International Journal of Physiology And Pathophysiology, 4(3), 253–259. doi: 10.1615/intjphyspathophys.v4.i3.70
  7. Schofield, Z. V., Woodruff, T. M., Halai, R., Wu, M. C., & Cooper, M. A. (2013). Neutrophils--a key component of ischemia-reperfusion injury. Shock, 40(6), 463–470. doi: 10.1097/shk.0000000000000044
  8. Pries, A., Kuebler, W., & Habazettl, H. (2018). Coronary Microcirculation in Ischemic Heart Disease. Current Pharmaceutical Design, 24(25), 2893–2899. doi: 10.2174/1381612824666180625142341
  9. Agrawal, V., Gupta, J., Qureshi, S., & Vishwakarma, V. (2016). Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart. Indian Heart Journal, 68(6), 856–861. doi: 10.1016/j.ihj.2016.06.010
  10. Kloner, R. (2013). Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction. Circulation Research, 113(4), 451–463. doi: 10.1161/circresaha.112.300627
  11. Heusch, G. (2013). Cardioprotection: chances and challenges of its translation to the clinic. The Lancet, 381(9861), 166–175. doi: 10.1016/s0140-6736(12)60916-7
  12. Spath, N., Mills, N., & Cruden, N. (2016). Novel cardioprotective and regenerative therapies in acute myocardial infarction: a review of recent and ongoing clinical trials. Future Cardiology, 12(6), 655–672. doi: 10.2217/fca-2016-0044
  13. Stone, G., Maehara, A., Witzenbichler, B., Godlewski, J.,
  14. Parise, H., Dambrink, J., et al. (2012). Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial InfarctionThe INFUSE-AMI Randomized Trial. JAMA, 307(17), 1817–1826. doi: 10.1001/jama.2012.421
  15. Thiele, H., Wöhrle, J., Hambrecht, R., Rittger, H., Birkemeyer, R., Lauer, B., et al. (2012). Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. The Lancet, 379(9819), 923–931. doi: 10.1016/s0140-6736(11)61872-2
  16. Ross, A., Gibbons, R., Stone, G., Kloner, R., & Alexander, R. (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. doi: 10.1016/j.jacc.2005.02.061
  17. Desmet, W., Bogaert, J., Dubois, C., Sinnaeve, P., Adriaenssens, T., Pappas, C., et al. (2010). High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction. European Heart Journal, 32(7), 867–877. doi: 10.1093/eurheartj/ehq492
  18. Fokkema, M., Vlaar, P., & Zijlstra, F. (2009). Response to Letter Regarding Article “Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial”. Circulation: Cardiovascular Interventions, 2(6). e6 doi: 10.1161/circinterventions.109.915942
  19. Fath-Ordoubadi, F., & Beatt, K. (1997). Glucose-Insulin-Potassium Therapy for Treatment of Acute Myocardial Infarction. Circulation, 96(4), 1152–1156. doi: 10.1161/01.cir.96.4.1152
  20. Díaz, R., Paolasso, E., Piegas, L., Tajer, C., Moreno, M., Corvalán, R., et al. (1998). Metabolic Modulation of Acute Myocardial Infarction. Circulation, 98(21), 2227–2234. doi: 10.1161/01.cir.98.21.2227
  21. Malmberg, K., Rydén, L., Efendic, S., Herlitz, J., Nicol, P., Waldenstrom, A., et al. (1995). Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year. Journal of The American College Of Cardiology, 26(1), 57–65. doi: 10.1016/0735-1097(95)00126-k
  22. Mamas, M., Deaton, C., Rutter, M., Yuille, M., Williams, S., Ray, S., et al. (2010). Impaired Glucose Tolerance and Insulin Resistance in Heart Failure: Underrecognized and Undertreated? Journal of Cardiac Failure, 16(9), 761–768. doi: 10.1016/j.cardfail.2010.05.027
  23. Selker, H. P., Beshansky, J. R., Sheehan, P. R., Massaro, J. M., Griffith, J. L., D'Agostino, R. B., et al. (2012). Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA, 307(18), 1925–33.
  24. Larson, A., Symons, J., & Jalili, T. (2012). Therapeutic Potential of Quercetin to Decrease Blood Pressure: Review of Efficacy and Mechanisms. Advances in Nutrition, 3(1), 39–46. doi: 10.3945/an.111.001271
  25. Chen, B., Wang, L., Huang, K., Wang, C., Chiang, C., & Liu, S. (2014). Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway. The Journal of Nutritional Biochemistry, 25(11), 1226–1234. doi: 10.1016/j.jnutbio.2014.05.013
  26. Lei, X., Chao, H., Zhang, Z., Lv, J., Li, S., Wei, H., et al. (2015). Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway. Molecular Medicine Reports, 12(3), 3688–3696. doi: 10.3892/mmr.2015.3857
  27. Tokyol, Ç., Yilmaz, S., Kahraman, A., Çakar, H., & Polat, C. (2006). The Effects of Desferrioxamine and Quercetin on Liver Injury Induced by Hepatic Ischaemia-Reperfusion in Rats. Acta Chirurgica Belgica, 106(1), 68–72. doi: 10.1080/00015458.2006.11679837
  28. Parkhomenko, A., Kozhukhov, S., Gurjeva, O. (2005). Clinical efficacy of intravenous lipoxygenase inhibitor quercetin in patients with acute ST-segment elevation myocardial infarction: results of a prospective randomized open-label trial. Seminars in Cardiology, 11(4), 154–158.
  29. Parkhomenko, А., Mojbenko, А., Kozhukhov, S., Irkin, О., Maksutona, N., Shklyar, L., & Shalamaj, A. (2000). Pervyj opyt primeneniya vnutrivennoj formy ingibitora 5-lipoksigenasy u bol'nykh s ostrym infarktom miokarda: kliniko-hemodinamicheskie paralleli, vliyanie preparata na razmery nekroza [The first experience of the use of the intravenous form of the 5-lipoxygenase inhibitor in patients with acute myocardial infarction: clinical and hemodynamic parallels, the effect of the drug on the size of necrosis]. Ukrainskyi kardiolohichnyi zhurnal, 1–2, 5–9. [in Russian].
  30. Parkhomenko, A., Kozhukhov, S., Irkin, O., Bryl, Z. H., Skarzhevsky, A., Solarik, O., & Shumakov, A. V. (2000). Cardioprotective effects of 5-lipoxigenase inhibitor quercetine in thrombolysed patients with acute myocardial infarction. European Heart Journal, 21, 476.
  31. Kozhukhov, S., & Parkhomenko, A. (2005). Does 5-lipoxygenase blockade impact future outcomes in patients with acute myocardial infarction? European Heart Journal, 26, 22.
  32. Parkhomenko, A., Kozhukhov, S., & Lutay, Y. (2018). Multicenter randomized clinical trial of the efficacy and safety of intravenous quercetin in patientswith ST-elevation acute myocardial infarction. European Heart Journal, 39(S1), 431. doi: 10.1093/eurheartj/ehy565.2152
  33. Dominguez-Rodriguez, A. (2010). Myocardial ischemia-reperfusion injury: Possible role of melatonin. World Journal of Cardiology, 2(8), 233. doi: 10.4330/wjc.v2.i8.233
  34. Galano, A., Tan, D., & Reiter, R. (2012). On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. Journal of Pineal Research, 54(3), 245–257. doi: 10.1111/jpi.12010
  35. Dominguez-Rodriguez, A., Abreu-Gonzalez, P., & Avanzas, P. (2012). The role of melatonin in acute myocardial infarction. Frontiers In Bioscience, 17(7), 2433–2441. doi: 10.2741/4063
  36. Dominguez-Rodriguez, A., Abreu-Gonzalez, P., de la Torre-Hernandez, J., Gonzalez-Gonzalez, J., Garcia-Camarero, T., Consuegra-Sanchez, L. et al. (2016). Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: Results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial. Journal o Pineal Research, 62(1), e12374. doi: 10.1111/jpi.12374
  37. Ibanez, B., Cimmino, G., Prat-González, S., Vilahur, G., Hutter, R., García, M., et al. (2011). The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion. International Journal of Cardiology, 147(3), 428–432. doi: 10.1016/j.ijcard.2009.09.551
  38. Khanal, S., & Vadivelu, R. (2014). Effect of early metoprolol on infarct size in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: The effect of metoprolol in cardioprotection during an acute myocardial infarction (METOCARD-CNIC) trial. Indian Heart Journal, 66(1), 127–128. doi: 10.1016/j.ihj.2013.12.044
  39. Landoni, G., Zangrillo, A., Lomivorotov, V., Likhvantsev, V., Ma, J., De Simone, F., & Fominskiy, E. (2016) Cardiac protection with phosphocreatine: a meta-analysis. Interactive CardioVascular and Thoracic Surgery, 23(4), 637–646. doi: 10.1093/icvts/ivw171
  40. Gaddi, A., Galuppo, P., & Yang, J. (2017). Creatine Phosphate Administration in Cell Energy Impairment Conditions: A Summary of Past and Present Research. Heart, Lung And Circulation, 26(10), 1026–1035. doi: 10.1016/j.hlc.2016.12.020
  41. Wu, M., Huang, Z., Xie, H., & Zhou, Z. (2013). Nicorandil in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis. Plos ONE, 8(10), e78231. doi: 10.1371/journal.pone.0078231
  42. Liu, T., & Feng, L. (2012). Postconditioning effect of oral nicorandil treatment on patients with acute anterior myocardial infarction. Heart, 98(Suppl 2), E8.1–E8. doi: 10.1136/heartjnl-2012-302920a.16
  43. Yu, S., Li, L., & Zhang, S. (2016). Clinical effect of intravenous thrombolysis combined with nicorandil therapy in patients with acute ST-segment elevation myocardial infarction. Tropical Journal of Pharmaceutical Research, 15(6), 1335. doi: 10.4314/tjpr.v15i6.29
  44. Kousholt, B., Rolighed Larsen, J., Bisgaard, L., Burnett, J., Hasenkam, J., & Goetze, J. (2012). Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion. Cardiovascular Endocrinology, 1(1), 4–12. doi: 10.1097/xce.0b013e328356c67b
  45. Ciapponi, A., Pizarro, R., & Harrison, J. (2005). Trimetazidine for stable angina. Cochrane Database of Systematic Reviews., 4. doi: 10.1002/14651858.CD003614.pub2
  46. McCarthy, C., Mullins, K., & Kerins, D. (2015). The role of trimetazidine in cardiovascular disease: beyond an anti-anginal agent. European Heart Journal - Cardiovascular Pharmacotherapy, 2(4), 266–272. doi: 10.1093/ehjcvp/pvv051
  47. (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 Heart Journal, 21(18), 1537–1546. doi: 10.1053/euhj.1999.2439
  48. Cung, T. T., Morel, O., Cayla, G., Rioufol, G., Garcia-Dorado, D., Angoulvant, D., et al. (2015). Cyclosporine before PCI in patients with acute myocardial infarction. New England Journal of Medicine, 373(11), 1021–1031. doi: 10.1056/NEJMoa1505489
  49. Mewton, N., Croisille, P., Gahide, G., Rioufol, G., Bonnefoy, E., Sanchez, I., et al. (2010). Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction. Journal of The American College of Cardiology, 55(12), 1200–1205. doi: 10.1016/j.jacc.2009.10.052
  50. Ottani, F., Latini, R., Staszewsky, L., La Vecchia, L., Locuratolo, N., Sicuro, M., et al. (2016). Cyclosporine A in Reperfused Myocardial Infarction. Journal of The American College of Cardiology, 67(4), 365–374. doi: 10.1016/j.jacc.2015.10.081
  51. Lønborg, J., Kelbæk, H., Vejlstrup, N., Bøtker, H., Kim, W., Holmvang, L., et al. (2012). Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia. Circulation: Cardiovascular Interventions, 5(2), 288–295. doi: 10.1161/circinterventions.112.968388
  52. Woo, J., Kim, W., Ha, S., Kim, J., Kim, S., Kim, W., et al. (2013). Cardioprotective Effects of Exenatide In Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention; Results of Exenatide Myocardial Protection in Revascularization (EMPIRE) Study. The American Journal of Cardiology, 111(7), 47B. doi: 10.1016/j.amjcard.2013.01.012
  53. Najjar, S. (2011). Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction. JAMA, 305(18), 1863. doi: 10.1001/jama.2011.592
  54. Suh, J., Chung, W., Kim, Y., Kim, K., Jeon, E., Cho, Y., et al. (2011). The effect of intravenous administration of erythropoietin on the infarct size in primary percutaneous coronary intervention. International Journal of Cardiology, 149(2), 216–220. doi: 10.1016/j.ijcard.2010.02.002
  55. Steppich, B., Groha, P., Ibrahim, T., Schunkert, H., Laugwitz, K., Hadamitzky, M., et al. (2017). Effect of Erythropoietiцn in patients with acute myocardial infarction: five-year results of the REVIVAL-3 trial. BMC Cardiovascular Disorders, 17(1). doi: 10.1186/s12872-016-0464-3
  56. Lefer, D., & Marbán, E. (2017). Is Cardioprotection Dead? Circulation, 136(1), 98–109. doi: 10.1161/circulationaha.116.027039
  57. Вøtker, H. E., Hausenloy, D., Andreadou, I., Antonucci, S., Boengler, K., Davidson, S. M., et al. (2018). Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic research in cardiology, 113(5), 39. doi: 10.1007/s00395-018-0696-8

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Kozhukhov SM, Parkhomenko OM. Pharmacological approaches to the prevention of myocardial ischemia-reperfusion injury in experimental study and clinical practice. Zaporozhye Medical Journal [Internet]. 2019Jul.15 [cited 2026May16];21(4). Available from: https://zmj.zsmu.edu.ua/article/view/173356

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Vol. 21 No. 4 (2019)

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Review

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