Роль микроваскулярной обструкции и внутримиокардиального кровоизлияния в реперфузионном повреждении сердца

Формирование микроваскулярной обструкции (МВО) коронарных артерий может способствовать увеличению смертности и развитию тяжелых осложнений у больных острым инфарктом миокарда (ОИМ), которым в дальнейшем проводилось чрескожное коронарное вмешательство (ЧКВ). Внутримиокардиальное кровоизлияние (ВМК) наблюдается у 41–50 % больных с инфарктом миокарда с подъемом сегмента ST и ЧКВ и сопровождается воспалением. Имеются данные о том, что микротромбы не участвуют в развитии МВО, которое ассоциировано с размером инфаркта, длительностью ишемии и отеком миокарда. Однако нет убедительных сведений о том, что последний играет важную роль в развитии МВО. Имеются доказательства того, что тромбоциты, воспаление, Ca2+-перегрузка, нейропептид Y и эндотелин-1 могут быть задействованы в патогенезе МВО. Под вопросом остается роль дисфункции эндотелиальных клеток в формировании МВО у больных с ОИМ и ЧКВ. Неясно, снижается ли выработка оксида азота у пациентов с МВО. Получены лишь косвенные данные об участии воспаления в развитии МВО. Роль активных форм кислорода, некроптоза и пироптоза в патогенезе МВО остается неизученной. Участие тромбоксана А2, вазопрессина и простациклина в развитии МВО ранее не исследовалось. Не получено убедительных доказательств роли спазма коронарных артерий в развитии МВО. Двойная антиагрегантная терапия повышает эффективность ЧКВ в предотвращении МВО. Неизвестно, способствуют ли адреналин или блокаторы Са2+-каналов L-типа улучшению коронарного кровотока у пациентов с МВО.

1. Majno G., Ames A., Chaing J., Wright R.L. No reflow after cerebral ischemia. Lancet. 1967;290(7515):569–570. doi: 10.1016/S0140-6736(67)90552-1

2. Kloner R.A., Ganote C.E., Jennings R.B. The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J. Clin. Invest. 1974;54(6):1496– 1508. doi: 10.1172/JCI107898

3. Schofer J., Montz R., Mathey D.G. Scintigraphic evidence of the “no reflow” phenomenon in human beings after coronary thrombolysis. J. Am. Coll. Cardiol. 1985;5(3):593–598. doi: 10.1016/s0735-1097(85)80381-8

4. McCartney P.J., Berry C. Redefining successful primary PCI. Eur. Heart J. Cardiovasc. Imaging. 2019;20(2):133–135. doi: 10.1093/ehjci/jey159

5. Cuculi F., Herring N., de Caterina A.R., Banning A.P., Prendergast B.D., Forfar J.C., Choudhury R.P., Channon K.M., Kharbanda R.K. Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction. Heart. 2013;99(16):1198–1203. doi: 10.1136/heartjnl-2012-303443

6. Feng C., Liu Y., Wang L., Niu D., Han B. Effects of early intracoronary administration of nicorandil during percutaneous coronary intervention in patients with acute myocardial infarction. Heart Lung Circ. 2019;28(6):858–865. doi: 10.1016/j.hlc.2018.05.097

7. Li Q., Zhao Y.G., Wang Z., Jiang H.P., Liu W.B., Cao B.F. Effects of first high-dose atorvastatin loading in patients with st-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Am. J. Ther. 2018;25(3):e291–e298. doi: 10.1097/MJT.0000000000000370

8. Ndrepepa G., Tiroch K., Fusaro M., Keta D., Seyfarth M., Byrne R.A., Pache J., Alger P., Mehilli J., Schömig A., Kastrati A. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J. Am. Coll. Cardiol. 2010;55(21):2383–2389. doi: 10.1016/j.jacc.2009.12.054

9. Rossington J.A., Sol E., Masoura K., Aznaouridis K., Chelliah R., Cunnington M., Davison B., John J., Oliver R., Hoye A. No-reflow phenomenon and comparison to the normal-flow population postprimary percutaneous coronary intervention for ST elevation myocardial infarction: case-control study (NORM PPCI). Open Heart. 2020;7(2):e001215. doi: 10.1136/openhrt-2019-001215

10. Maznyczka A.M., McCartney P.J., Oldroyd K.G., Lindsay M., McEntegart M., Eteiba H., Rocchiccioli P., Good R., Shaukat A., Robertson K., … Berry C. Effects of intracoronary alteplase on microvascular function in acute myocardial infarction. J. Am. Heart Assoc. 2020;9(3):e014066. doi: 10.1161/JAHA.119.014066

11. Maznyczka A.M., McCartney P., Duklas P., McEntegart M., Oldroyd K.G., Greenwood J.P., Muir D., Chowdhary S., Gershlick A.H., Appleby C., … Trial of low-dose adjunctive alTeplase during primary PCI) investigators. Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial. Heart. 2021:heartjnl-2020-317828. doi: 10.1136/heartjnl-2020-317828

12. Bonfig N.L., Soukup C.R., Shah A.A., Davidson S.J., Stanberry L.I., Okeson B.K., Traverse J.H. Circadian dependence of microvascular obstruction during ST-segment elevation myocardial infarction. Int. J. Cardiol. 2022;366:25–29. doi: 10.1016/j.ijcard.2022.07.012

13. Holzknecht M., Tiller C., Reindl M., Lechner I., Troger F., Hosp M., Mayr A., Brenner C., Klug G., Bauer A., Metzler B., Reinstadler S.J. C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction. Int. J. Cardiol. 2021;338:30–36. doi: 10.1016/j.ijcard.2021.06.023

14. Ma M., Diao K.Y., Yang Z.G., Zhu Y., Guo Y.K., Yang M.X., Zhang Y., He Y. Clinical associations of microvascular obstruction and intramyocardial hemorrhage on cardiovascular magnetic resonance in patients with acute ST segment elevation myocardial infarction (STEMI): An observational cohort study. Medicine (Baltimore). 2018;97(30):e11617. doi: 10.1097/MD.0000000000011617

15. Tarantini G., Razzolini R., Cacciavillani L., Bilato C., Sarais C., Corbetti F., Marra M.P., Napodano M., Ramondo A., Iliceto S. Influence of transmurality, infarct size, and severe microvascular obstruction on left ventricular remodeling and function after primary coronary angioplasty. Am. J. Cardiol. 2006;98(8):1033– 1040. doi: 10.1016/j.amjcard.2006.05.022

16. Berry C., Ibáñez B. Intramyocardial hemorrhage: the final frontier for preventing heart failure post-myocardial infarction. J. Am. Coll. Cardiol. 2022;79(1):49–51. doi: 10.1016/j.jacc.2021.11.002

17. Ma Q., Ma Y., Wang X., Li S., Yu T., Duan W., Wu J., Wen Z., Jiao Y., Sun Z., Hou Y. Intracoronary compared with intravenous bolus tirofiban on the microvascular obstruction in patients with STEMI undergoing PCI: a cardiac MR study. Int. J. Cardiovasc. Imaging. 2020;36(6):1121–1132. doi: 10.1007/s10554-020-01800-0

18. Zajdel W., Miszalski-Jamka T., Zalewski J., Legutko J., Żmudka K., Paszek E. Cardiac magnetic resonance shows improved outcomes in patients with an st-segment elevation myocardial infarction and a high thrombus burden treated with adjuvant aspiration thrombectomy. J. Clin. Med. 2022;11(17):5000. doi: 10.3390/jcm11175000

19. Zia M.I., Ghugre N.R., Roifman I., Strauss B.H., Walcarius R., Mohammed M., Sparkes J.D., Dick A.J., Wright G.A., Connelly K.A. Comparison of the frequencies of myocardial edema determined by cardiac magnetic resonance in diabetic versus nondiabetic patients having percutaneous coronary intervention for ST elevation myocardial infarction. Am. J. Cardiol. 2014;113(4):607–612. doi: 10.1016/j.amjcard.2013.10.040

20. Lechner I., Reindl M., Tiller C., Holzknecht M., Fink P., Troger F., Angerer G., Angerer S., Henninger B., Mayr A., … Reinstadler S.J. Temporal trends in infarct severity outcomes in st-segment-elevation myo cardial infarction: a cardiac magnetic resonance imaging study. J. Am. Heart Assoc. 2023;12(15):e028932. doi: 10.1161/JAHA.122.028932

21. Mayr A., Klug G., Schocke M., Trieb T., Mair J., Pedarnig K., Pachinger O., Jaschke W., Metzler B. Late microvascular obstruction after acute myocardial infarction: relation with cardiac and inflammatory markers. Int. J. Cardiol. 2012;157(3):391–396. doi: 10.1016/j.ijcard.2010.12.090

22. Ober C.D., Ober M.C., Iancu A.C. Serial transthoracic coronary Doppler shows complete reversibility of microvascular obstruction pattern at one month after reperfused acute myocardial infarction. Med. Ultrason. 2017;19(1):45–50. doi: 10.11152/mu-941

23. Алексеева Я.В., Вышлов Е.В., Павлюкова Е.Н., Усов В.Ю., Марков В.А., Рябов В.В. Влияние разных фенотипов микрососудистого повреждения миокарда на сократительную функцию левого желудочка у пациентов с инфарктом миокарда с подъемом сегмента ST. Кардиология. 2021;61(5):23– 31. doi: 10.18087/cardio.2021.5.n1500

24. Abbo K.M., Dooris M., Glazier S., O’Neill W.W., Byrd D., Grines C.L., Safian R.D. Features and outcome of no-reflow after percutaneous coronary intervention. Am. J. Cardiol. 1995;75(12):778– 782. doi: 10.1016/s0002-9149(99)80410-x

25. Wu K.C., Zerhouni E.A., Judd R.M., Lugo-Olivieri C.H., Barouch L.A., Schulman S.P., Blumenthal R.S., Lima J.A. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998;97(8):765–772. doi: 10.1161/01.cir.97.8.765

26. Romano M., Buffoli F., Lettieri C., Aroldi M., Tomasi L., Baccaglioni N., Rosiello R., Zanini R. No reflow in patients undergoing primary angioplasty for acute myocardial infarction at high risk: incidence and predictive factors. Minerva Cardioangiol. 2005;53(1):7–14.

27. Kim M.C., Cho J.Y., Jeong H.C., Lee K.H., Park K.H., Sim D.S., Yoon N.S., Youn H.J., Kim K.H., Hong Y.J., … Ahn Y. Long-term clinical outcomes of transient and persistent no reflow phenomena following percutaneous coronary intervention in patients with acute myocardial infarction. Korean Circ. J. 2016;46(4):490–498. doi: 10.4070/kcj.2016.46.4.490

28. Galiuto L., Garramone B., Scarà A., Rebuzzi A.G., Crea F., La Torre G., Funaro S., Madonna M., Fedele F., Agati L. AMICI Investigators. The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: results of the multicenter AMICI study. J. Am. Coll. Cardiol. 2008;51(5):552–559. doi: 10.1016/j.jacc.2007.09.051

29. Klug G., Mayr A., Schenk S., Esterhammer R., Schocke M., Nocker M., Jaschke W., Pachinger O., Metzler B. Prognostic value at 5 years of microvascular obstruction after acute myocardial infarction assessed by cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 2012;14(1):46. doi: 10.1186/1532-429X14-46

30. Kitabata H., Kubo T., Ishibashi K., Komukai K., Tanimoto T., Ino Y., Kashiwagi M., Ozaki Y., Shiono Y., Shimamura K., … Akasaka T. Prognostic value of microvascular resistance index immediately after primary percutaneous coronary intervention on left ventricular remodeling in patients with reperfused anterior acute ST-segment elevation myocardial infarction. JACC Cardiovasc. Interv. 2013;6(10):1046–1054. doi: 10.1016/j.jcin.2013.05.014

31. Khorramirouz R., Corban M.T., Yang S.W., Lewis B.R., Bois J., Foley T., Lerman L.O., Herrmann J., Oh J.K., Lerman A. Microvascular obstruction in non-infarct related coronary arteries is an independent predictor of major adverse cardiovascular events in patients with ST segment-elevation myocardial infarction. Int. J. Cardiol. 2018;273:22–28. doi: 10.1016/j.ijcard.2018.08.020

32. Marcos-Garcés V., Perez N., Gavara J., Lopez-Lereu M.P., Monmeneu J.V., Rios-Navarro C., de Dios E., Merenciano-González H., Gabaldon-Pérez A., Cànoves J., … Bodi V. Risk score for early risk prediction by cardiac magnetic resonance after acute myocardial infarction. Int. J. Cardiol. 2022;349:150–154. doi: 10.1016/j.ijcard.2021.11.050

33. Pezel T., Besseyre des Horts T., Schaaf M., Croisille P., Bière L., Garcia-Dorado D., Jossan C., Roubille F., Cung T.T., Prunier F., … Mewton N. Predictive value of early cardiac magnetic resonance imaging functional and geometric indexes for adverse left ventricular remodelling in patients with anterior ST-segment elevation myocardial infarction: A report from the CIRCUS study. Arch. Cardiovasc. Dis. 2020;113(11):710–720. doi: 10.1016/j.acvd.2020.05.024

34. Reindl M., Stiermaier T., Lechner I., Tiller C., Holzknecht M., Mayr A., Schwaiger J.P., Brenner C., Klug G., Bauer A., … Reinstadler S.J. Cardiac magnetic resonance imaging improves prognostic stratification of patients with ST-elevation myocardial infarction and preserved ejection fraction. Eur. Heart J. Open. 2021;1(3):oeab033. doi: 10.1093/ehjopen/oeab033

35. Russo M., Montone R.A., D’Amario D., Camilli M., Canonico F., Santamaria C., Iannaccone G., Pedicino D., Pidone C., Galli M., … Crea F. Role of perilipin 2 in microvascular obstruction in patients with ST-elevation myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care. 2021;10(6):633–642. doi: 10.1093/ehjacc/zuaa004

36. Zhang M., Lu Y., Li Z., Shao Y., Chen L., Yang Y., Xi J., Chen M., Jiang T. Value of fast MVO identification from contrast-enhanced cine (CE-SSFP) combined with myocardial strain in predicting adverse events in patients after st-elevation myocardial infarction. Front. Cardiovasc. Med. 2022;8:804020. doi: 10.3389/fcvm.2021.804020

37. Porto I., Biasucci L.M., de Maria G.L., Leone A.M., Niccoli G., Burzotta F., Trani C., Tritarelli A., Vergallo R., Liuzzo G., Crea F. Intracoronary microparticles and microvascular obstruction in patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. Eur. Heart J. 2012;33(23):2928–2938. doi: 10.1093/eurheartj/ehs065

38. McCartney P.J., Eteiba H., Maznyczka A.M., McEntegart M., Greenwood J.P., Muir D.F., Chowdhary S., Gershlick A.H., Appleby C., Cotton J.M., … T-TIME Group. Effect of low-dose intracoronary alteplase during primary percutaneous coronary intervention on microvascular obstruction in patients with acute myocardial infarction: a randomized clinical trial. JAMA. 2019;321(1):56–68. doi: 10.1001/jama.2018.19802

39. Jesel L., Morel O., Ohlmann P., Germain P., Faure A., Jahn C., Coulbois P.M., Chauvin M., Bareiss P., Roul G. Role of pre-infarction angina and inflammatory status in the extent of microvascular obstruction detected by MRI in myocardial infarction patients treated by PCI. Int. J. Cardiol. 2007;121(2):139–147. doi: 10.1016/j.ijcard.2006.10.022

40. Bloom J.E., Andrew E., Nehme Z., Dinh D.T., Fernando H., Shi W.Y., Vriesendorp P., Nanayakarra S., Dawson L.P., Brennan A., … Stub D. Pre-hospital heparin use for ST-elevation myocardial infarction is safe and improves angiographic outcomes. Eur. Heart J. Acute Cardiovasc. Care. 2021;10(10):1140–1147. doi: 10.1093/ehjacc/zuab032

41. Zalewski J., Durak M., Lech P., Gajos G., Undas A., Nessler J., Rosławiecka A., Zmudka K. Platelet activation and microvascular injury in patients with ST-segment elevation myocardial infarction. Kardiol. Pol. 2012;70(7):677–684.

42. Basili S., Tanzilli G., Raparelli V., Calvieri C., Pignatelli P., Carnevale R., Dominici M., Placanica A., Arrivi A., Farcomeni A., Barillà F., Mangieri E., Violi F. Aspirin reload before elective percutaneous coronary intervention: impact on serum thromboxane b2 and myocardial reperfusion indexes. Circ. Cardiovasc. Interv. 2014;7(4):577–584. doi: 10.1161/CIRCINTERVENTIONS.113.001197

43. Aitmokhtar O., Paganelli F., Benamara S., Azaza A., Bonello L., Hamza O., Seddiki S., Benathmane T., Saidane M., Bouzid A., … Benkhedda S. Impact of platelet inhibition level on subsequent no-reflow in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Arch. Cardiovasc. Dis. 2017;110(11):626– 633. doi: 10.1016/j.acvd.2016.12.017

44. Lee S.R., Jung J.M., Jung L.Y., Lee J.H., Lee S.H., Rhee K.S., Chae J.K., Kim W.H., Ko J.K., Lee D.H., Rosenson R.S. Elevated coronary whole blood viscosity in acute coronary syndrome patients. Clin. Hemorheol. Microcirc. 2013;55(1):85–94. doi: 10.3233/CH-131692

45. Fracassi F., Vetrugno V., Mandurino-Mirizzi A., Cosentino N., Panicale S., Caprari P., Niccoli G., Crea F. Effect of hemorheological parameters on myocardial injury after primary or elective percutaneous coronary intervention. Coron. Artery Dis. 2018;29(8):638–646. doi: 10.1097/MCA.0000000000000661

46. Ghaleh B., Dubois-Randé J.L., Hittinger L., Giudicelli J.F., Berdeaux A. Comparisons of the effects of nicorandil, pinacidil, nicardipine and nitroglycerin on coronary vessels in the conscious dog: role of the endothelium. Br. J. Pharmacol. 1995;114(2):496–502. doi: 10.1111/j.1476-5381.1995.tb13254.x

47. Abebe W., Makujina S.R., Mustafa S.J. Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium. Am. J. Physiol. 1994;266(5 Pt 2):H2018–H2025. doi: 10.1152/ajpheart.1994.266.5.H2018

48. Toda N., Matsumoto T., Yoshida K. Comparison of hypoxia-induced contraction in human, monkey, and dog coronary arteries. Am. J. Physiol. 1992;262(3Pt2):H678–H683. doi: 10.1152/ajpheart.1992.262.3.H678

49. Abdelaziz H.K., Elkilany W., Khalid S., Sabet S., Saad M. Efficacy and safety of intracoronary verapamil versus sodium nitroprusside for the prevention of microvascular obstruction during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Coron. Artery Dis. 2017;28(1):11– 16. doi: 10.1097/MCA.0000000000000423

50. Piana R.N., Paik G.Y., Moscucci M., Cohen D.J., Gibson C.M., Kugelmass A.D., Carrozza J.P. Jr., Kuntz R.E., Baim D.S. Incidence and treatment of ‘no-reflow’ after percutaneous coronary intervention. Circulation. 1994;89(6):2514–2518. doi: 10.1161/01.cir.89.6.2514

51. Wang H.J., Lo P.H., Lin J.J., Lee H., Hung J.S. Treatment of slow/no-reflow phenomenon with intracoronary nitroprusside injection in primary coronary intervention for acute myocardial infarction. Catheter. Cardiovasc. Interv. 2004;63(2):171–176. doi: 10.1002/ccd.20149

52. Nazir S.A., McCann G.P., Greenwood J.P., Kunadian V., Khan J.N., Mahmoud I.Z., Blackman D.J., Been M., Abrams K.R., Shipley L., Wilcox R., Adgey A.A., Gershlick A.H. Strategies to attenuate microvascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial. Eur. Heart J. 2016;37(24):1910–1919. doi: 10.1093/eurheartj/ehw136

53. Niccoli G., Rigattieri S., de Vita M.R., Valgimigli M., Corvo P., Fabbiocchi F., Romagnoli E., de Caterina A.R., La Torre G., Lo Schiavo P., … Crea F. Open-label, randomized, placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction: the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction). JACC Cardiovasc. Interv. 2013;6(6):580–589. doi: 10.1016/j.jcin.2013.02.009

54. Taylor A.J., Bobik A., Richards M., Kaye D., Raines G., Gould P., Jennings G. Myocardial endothelin-1 release and indices of inflammation during angioplasty for acute myocardial infarction and stable coronary artery disease. Am. Heart J. 2004;148(2):e10. doi: 10.1016/j.ahj.2004.03.018

55. Eitel I., Nowak M., Stehl C., Adams V., Fuernau G., Hildebrand L., Desch S., Schuler G., Thiele H. Endothelin-1 release in acute myocardial infarction as a predictor of long-term prognosis and no-reflow assessed by contrast-enhanced magnetic resonance imaging. Am. Heart J. 2010;159(5):882–890. doi: 10.1016/j.ahj.2010.02.019

56. Tan C.M.J., Green P., Tapoulal N., Lewandowski A.J., Leeson P., Herring N. The role of neuropeptide y in cardiovascular health and disease. Front. Physiol. 2018;9:1281. doi: 10.3389/fphys.2018.01281

57. Clarke J.G., Davies G.J., Kerwin R., Hackett D., Larkin S., Dawbarn D., Lee Y., Bloom S.R., Yacoub M., Maseri A. Coronary artery infusion of neuropeptide Y in patients with angina pectoris. Lancet. 1987;1(8541):1057–1059. doi: 10.1016/s0140-6736(87)90483-1

58. Herring N., Tapoulal N., Kalla M., Ye X., Borysova L., Lee R., Dall’Armellina E., Stanley C., Ascione R., Lu C.J., … Oxford Acute Myocardial Infarction (OxAMI) Study. Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction. Eur. Heart J. 2019;40(24):1920–1929. doi: 10.1093/eurheartj/ehz115

59. Gutstein W.H., Anversa P., Guideri G. Coronary artery spasm: involvement of small intramyocardial branches. Atherosclerosis. 1987;67(1):1–7. doi: 10.1016/0021-9150(87)90258-9

60. Sellke N., Kuczmarski A., Lawandy I., Cole V.L., Ehsan A., Singh A.K., Liu Y., Sellke F.W., Feng J. Enhanced coronary arteriolar contraction to vasopressin in patients with diabetes after cardiac surgery. J. Thorac. Cardiovasc. Surg. 2018;156(6):2098–2107. doi: 10.1016/j.jtcvs.2018.05.090

61. Aksu T., Guler T.E., Colak A., Baysal E., Durukan M., Sen T., Guray U. Intracoronary epinephrine in the treatment of refractory no-reflow after primary percutaneous coronary intervention: a retrospective study. BMC Cardiovasc. Disord. 2015;15:10. doi: 10.1186/s12872-015-0004-6

62. Navarese E.P., Frediani L., Kandzari D.E., Caiazzo G., Cenname A.M., Cortese B., Piva T., Muçaj A., Tumscitz C., Paparoni F., … Kubica J. Efficacy and safety of intracoronary epinephrine versus conventional treatments alone in STEMI patients with refractory coronary no-reflow during primary PCI: The RESTORE observational study. Catheter. Cardiovasc. Interv. 2021;97(4):602–611. doi: 10.1002/ccd.29113

63. Darwish A., Frere A.F., Abdelsamie M., Awady W.E., Gouda M. Intracoronary epinephrine versus adenosine in the management of refractory no-reflow phenomenon: a single-center retrospective cohort study. Ann. Saudi. Med. 2022;42(2):75–82. doi: 10.5144/0256-4947.2022.75

64. Zhao J., Yang Y., You S., Cui C., Gao R. Carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion. Int. J. Cardiol. 2007;115(3):334–341. doi: 10.1016/j.ijcard.2006.03.017

65. Ito H., Taniyama Y., Iwakura K., Nishikawa N., Masuyama T., Kuzuya T., Hori M., Higashino Y., Fujii K., Minamino T. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J. Am. Coll. Cardiol. 1999;33(3):654–660. doi: 10.1016/s0735-1097(98)00604-4

66. Bolognese L., Carrabba N., Parodi G., Santoro G.M., Buonamici P., Cerisano G., Antoniucci D. Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation. 2004;109(9):1121–1126. doi: 10.1161/01.CIR.0000118496.44135.A7

67. Chen B.H., An D.A., He J., Xu J.R., Wu L.M., Pu J. Myocardial extracellular volume fraction allows differentiation of reversible versus irreversible myocardial damage and prediction of adverse left ventricular remodeling of st-elevation myocardial infarction. J. Magn. Reson. Imaging. 2020;52(2):476–487. doi: 10.1002/jmri.27047

68. Tiller C., Reindl M., Holzknecht M., Lechner I., Schwaiger J., Brenner C., Mayr A., Klug G., Bauer A., Metzler B., Reinstadler S.J. Association of plasma interleukin-6 with infarct size, reperfusion injury, and adverse remodelling after ST-elevation myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care. 2022;11(2):113–123. doi: 10.1093/ehjacc/zuab110

69. Dregoesc M.I., Iancu A.C., Ober C.D., Homorodean C., Bãlãnescu Ş., Bolboacã S. In ST-segment elevation myocardial infarction, the echocardiographic parameters of microvascular obstruction are not associated with left ventricular remodeling at five years of follow-up. Echocardiography. 2019;36(6):1103–1109. doi: 10.1111/echo.14371

70. Tsujioka H., Imanishi T., Ikejima H., Tanimoto T., Kuroi A., Kashiwagi M., Okochi K., Ishibashi K., Komukai K., Ino Y., Kitabata H., Akasaka T. Post-reperfusion enhancement of CD14(+)CD16(-) monocytes and microvascular obstruction in ST-segment elevation acute myocardial infarction. Circ. J. 2010;74(6):1175– 1182. doi: 10.1253/circj.cj-09-1045

71. Shetelig C., Limalanathan S., Hoffmann P., Seljeflot I., Gran J.M., Eritsland J., Andersen G.Ø. Association of IL-8 with infarct size and clinical outcomes in patients with STEMI. J. Am. Coll. Cardiol. 2018;72(2):187–198. doi: 10.1016/j.jacc.2018.04.053

72. Ota S., Tanimoto T., Orii M., Hirata K., Shiono Y., Shimamura K., Matsuo Y., Yamano T., Ino Y., Kitabata H., … Akasaka T. Association between hyperglycemia at admission and microvascular obstruction in patients with ST-segment elevation myocardial infarction. J. Cardiol. 2015;65(4):272–277. doi: 10.1016/j.jjcc.2014.10.013

73. Beijnink C.W.H., van der Hoeven N.W., Konijnenberg L.S.F., Kim R.J., Bekkers S.C.A.M., Kloner R.A., Everaars H., El Messaoudi S., van Rossum A.C., van Royen N., Nijveldt R. Cardiac MRI to visualize myocardial damage after ST-segment elevation myocardial infarction: a review of its histologic validation. Radiology. 2021;301(1):4–18. doi: 10.1148/radiol.2021204265

74. Fernández-Jiménez R., Galán-Arriola C., Sánchez-González J., Agüero J., López-Martín G.J., Gomez-Talavera S., Garcia-Prieto J., Benn A., MolinaIracheta A., Barreiro-Pérez M., … Ibanez B. Effect of ischemia duration and protective interventions on the temporal dynamics of tissue composition after myocardial infarction. Circ. Res. 2017;121(4):439–450. doi: 10.1161/CIRCRESAHA.117.310901

75. Bonfig N.L., Soukup C.R., Shah A.A., Olet S., Davidson S.J., Schmidt C.W., Peterson R., Henry T.D., Traverse J.H. Increasing myocardial edema is associated with greater microvascular obstruction in ST-segment elevation myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 2022;323(4):H818–H824. doi: 10.1152/ajpheart.00347.2022

76. Bochaton T., Lassus J., Paccalet A., Derimay F., Rioufol G., Prieur C., Bonnefoy-Cudraz E., Crola Da Silva C., Bernelin H., Amaz C., … Mewton N. Association of myocardial hemorrhage and persistent microvascular obstruction with circulating inflammatory biomarkers in STEMI patients. PLoS One. 2021;16(1):e0245684. doi: 10.1371/journal.pone.0245684

77. Xu Z., Chen W., Zhang R., Wang L., Chen R., Zheng J., Gao F. Human recombinant apyrase therapy protects against myocardial ischemia/reperfusion injury and preserves left ventricular systolic function in rats, as evaluated by 7T cardiovascular magnetic resonance imaging. Korean J. Radiol. 2020;21(6):647–659. doi: 10.3348/kjr.2019.0853

78. Ibanez B., Aletras A.H., Arai A.E., Arheden H., Bax J., Berry C., Bucciarelli-Ducci C., Croisille P., Dall’Armellina E., Dharmakumar R., … Fuster V. Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC scientific expert panel. J. Am. Coll. Cardiol. 2019;74(2):238–256. doi: 10.1016/j.jacc.2019.05.024

79. Massalha E., Oren D., Goitein O., Brodov Y., Fardman A., Younis A., Berkovitch A., Raibman-Spector S., Konen E., Maor E., … Matetzky S. Post-STsegment-elevation myocardial infarction platelet reactivity is associated with the extent of microvascular obstruction and infarct size as determined by cardiac magnetic resonance imaging. J. Am. Heart Assoc. 2022;11(3):e020973. doi: 10.1161/JAHA.121.020973

80. Khan J.N., Greenwood J.P., Nazir S.A., Lai F.Y., Dalby M., Curzen N., Hetherington S., Kelly D.J., Blackman D., Peebles C., … McCann G.P. Infarct size following treatment with second- versus third-generation P2Y12 antagonists in patients with multivessel coronary disease at ST-segment elevation myocardial infarction in the CvLPRIT study. J. Am. Heart Assoc. 2016;5(6):e003403. doi: 10.1161/JAHA.116.003403

81. Naghshtabrizi N., Sajedi M., Naghshtabrizi B., Mozayanimonfared A., Ali Seif Rabiei M., Kanonisabet A. Randomized trial of intracoronary adenosine as adjunctive therapy for prevention of the no-reflow phenomenon. Coron. Artery Dis. 2020;31(6):527–529. doi: 10.1097/MCA.0000000000000863

82. Aetesam-Ur-Rahman M., Brown A.J., Jaworski C., Giblett J.P., Zhao T.X., Braganza D.M., Clarke S.C., Agrawal B.S.K., Bennett M.R., West N.E.J., Hoole S.P. Adenosine-induced coronary steal is observed in patients presenting with ST-segment-elevation myocardial infarction. J. Am. Heart Assoc. 2021;10(13):e019899. doi: 10.1161/JAHA.120.019899

83. Knabb R.M., Ely S.W., Bacchus A.N., Rubio R., Berne R.M. Consistent parallel relationships among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration with various interventions and beta-blockade in the dog. Circ. Res. 1983;53(1):33–41. doi: 10.1161/01.res.53.1.33

84. Buffington C.W., Feigl E.O. Adrenergic coronary vasoconstriction in the presence of coronary stenosis in the dog. Circ. Res. 1981;48(3):416–423. doi: 10.1161/01.res.48.3.416

85. Golino P., Maroko P.R., Carew T.E. The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion. Circulation. 1987;75(1):292– 298. doi: 10.1161/01.cir.75.1.292

86. Fu Q., Lu W., Huang Y.J., Wu Q., Wang L.G., Wang H.B., Jiang S.Z., Wang Y.J. Verapamil reverses myocardial no-reflow after primary percutaneous coronary intervention in patients with acute myocardial infarction. Cell. Biochem. Biophys. 2013;67(3):911–914. doi: 10.1007/s12013-013-9581-0