sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20240201sibmed-1454Research ArticleОБЗОРЫREVIEWSРоль микроваскулярной обструкции и внутримиокардиального кровоизлияния в реперфузионном повреждении сердцаThe role of microvascular obstruction and intramyocardial hemorrhage in reperfusion injury to the hearthttps://orcid.org/0000-0002-1513-8614ЗавадовскийК. В.ZavadovskyК. V.

Завадовский Константин Валерьевич, д.м.н.

634012, г. Томск, ул. Киевская, 111а 

Konstantin V. Zavadovsky, doctor of medical sciences

634012, Tomsk, Kievskaya st., 111a 

konstz@cardio-tomsk.ruhttps://orcid.org/0000-0003-1808-556XМухомедзяновА. В.MukhomedzyanovА. V.

Мухомедзянов Александр Валерьевич, к.м.н.

634012, г. Томск, ул. Киевская, 111а 

Alexandr V. Mukhomedzyanov, candidate of medical sciences

634012, Tomsk, Kievskaya st., 111a

sasha_m91@mail.ruhttps://orcid.org/0000-0002-6020-1598МасловЛ. Н.MaslovL. N.

Маслов Леонид Николаевич, д.м.н.

634012, г. Томск, ул. Киевская, 111а 

Leonid N. Maslov, doctor of medical sciences, professor

634012, Tomsk, Kievskaya st., 111a 

maslov@cardio-tomsk.ruhttps://orcid.org/0000-0002-6020-1598ВышловЕ. В.VyshlovЕ. V.

Вышлов Евгений Викторович, д.м.н.

634012, г. Томск, ул. Киевская, 111а

Evgeny V. Vyshlov, doctor of medical sciences

634012, Tomsk, Kievskaya st., 111a

evv@cardio-tomsk.ruhttps://orcid.org/0000-0002-7502-7502МочулаО. В.MochulaО. V.

Мочула Ольга Витальевна, к.м.н.

634012, г. Томск, ул. Киевская, 111а 

Olga V. Mochula, candidate of medical sciences

634012, Tomsk, Kievskaya st., 111a 

mochula.olga@gmail.comhttps://orcid.org/0000-0002-4502-0836СиротинаМ. А.SirotinaМ. А.

Сиротина Мария Александровна

634012, г. Томск, ул. Киевская, 111а 

Maria A. Sirotina

634012, Tomsk, Kievskaya st., 111a 

sirotina_maria@mail.ruhttps://orcid.org/0000-0002-6158-026XРюмшинаН. И.RyumshinaN. I.

Рюмшина Надежда Игоревна, к.м.н.

634012, г. Томск, ул. Киевская, 111а 

Nadezhda I. Ryumshina, candidate of medical sciences

634012, Tomsk, Kievskaya st., 111a 

n.rumshina@list.ruhttps://orcid.org/0000-0002-4871-3283МаксимоваА. С.MaksimovaА. S.

Максимова Александра Сергеевна, к.м.н.

634012, г. Томск, ул. Киевская, 111а

Aleksandra S. Maksimova, candidate of medical sciences

634012, Tomsk, Kievskaya st., 111a

asmaximova@yandex.ruhttps://orcid.org/0000-0002-6418-1643КанА. С.KanА. S.

Кан Артур Семенович

634012, г. Томск, ул. Киевская, 111а 

Artur S. Kan

634012, Tomsk, Kievskaya st., 111a 

kan989817@gmail.comhttps://orcid.org/0009-0004-2215-5414СлидневскаяА. С.SlidnevskayaА. S.

Слидневская Алиса Сергеевна

634012, г. Томск, ул. Киевская, 111а 

Alisa S. Slidnevskaya

634012, Tomsk, Kievskaya st., 111a 

alisaslidnevskaa@gmail.comНИИ кардиологии – филиал Томского национального исследовательского медицинского центра РАНРоссияCardiology Research Institute – Branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”Russian Federation202426042024442618Copyright © Завадовский К.В., Мухомедзянов А.В., Маслов Л.Н., Вышлов Е.В., Мочула О.В., Сиротина М.А., Рюмшина Н.И., Максимова А.С., Кан А.С., Слидневская А.С., 20242024Завадовский К.В., Мухомедзянов А.В., Маслов Л.Н., Вышлов Е.В., Мочула О.В., Сиротина М.А., Рюмшина Н.И., Максимова А.С., Кан А.С., Слидневская А.С.Zavadovsky К.V., Mukhomedzyanov А.V., Maslov L.N., Vyshlov Е.V., Mochula О.V., Sirotina М.А., Ryumshina N.I., Maksimova А.S., Kan А.S., Slidnevskaya А.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/1454

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.

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41–50 % of patients with ST-segment elevation myocardial infarction and PCI and is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO, which is associated with infarct size, the duration of ischemia, and myocardial edema. However, there is no conclusive evidence that the latter plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell dysfunction in MVO formation in patients with AMI and PCI remains under question. It is unclear whether nitric oxide production is decreased in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of reactive oxygen species, necroptosis and pyroptosis in the pathogenesis of MVO is also not studied. The participation of thromboxane A2, vasopressin, and prostacyclin in the formation of MVO is unknown. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca2+-channel blockers improves coronary blood flow in patients with MVO.

сердцеишемияреперфузиямикроваскулярная обструкцияфеномен no-reflowheartischemiareperfusionmicrovascular obstructionno-reflow phenomenonРабота выполнена при финансовой поддержке гранта Российского научного фонда № 23- 65-10017. Раздел, посвященный внутримиокардиальному кровоизлиянию, подготовлен в рамках государственного задания 122020300042-4.The study was supported by the Russian Science Foundation, grant No. 23-65-10017. The section on intramyocardial hemorrhage was prepared in the framework of the state assignment 122020300042-4.ReferencesMajno 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)90552-1Majno 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)90552-1Kloner 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/JCI107898Kloner 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/JCI107898Schofer 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)80381-8Schofer 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)80381-8McCartney P.J., Berry C. Redefining successful primary PCI. Eur. Heart J. Cardiovasc. Imaging. 2019;20(2):133–135. doi: 10.1093/ehjci/jey159McCartney P.J., Berry C. Redefining successful primary PCI. Eur. Heart J. Cardiovasc. Imaging. 2019;20(2):133–135. doi: 10.1093/ehjci/jey159Cuculi 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-2012-303443Cuculi 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-2012-303443Feng 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.2018.05.097Feng 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.2018.05.097Li 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.0000000000000370Li 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.0000000000000370Ndrepepa 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.2009.12.054Ndrepepa 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.2009.12.054Rossington 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-2019-001215Rossington 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-2019-001215Maznyczka 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.119.014066Maznyczka 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.119.014066Maznyczka 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-2020-317828Maznyczka 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-2020-317828Bonfig 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.2022.07.012Bonfig 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.2022.07.012Holzknecht 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.2021.06.023Holzknecht 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.2021.06.023Ma 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.0000000000011617Ma 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.0000000000011617Tarantini 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.2006.05.022Tarantini 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.2006.05.022Berry 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.2021.11.002Berry 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.2021.11.002Ma 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/s10554-020-01800-0Ma 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/s10554-020-01800-0Zajdel 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/jcm11175000Zajdel 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/jcm11175000Zia 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.2013.10.040Zia 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.2013.10.040Lechner 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.122.028932Lechner 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.122.028932Mayr 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.2010.12.090Mayr 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.2010.12.090Ober 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-941Ober 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-941Алексеева 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.n1500Alekseeva Ya.V., Vyshlov E.V., Pavlyukova E.N., Usov V.Yu., Markov V.A., Ryabov V.V. Impact of microvascular injury various types on function of left ventricular in patients with primary myocardial infarction with ST segment elevation. Kardiologiya = Cardiology. 2021;61(5):23–31. [In Russian]. doi: 10.18087/cardio.2021.5.n1500Abbo 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-xAbbo 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-xWu 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.97.8.765Wu 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.97.8.765Romano 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.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.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.2016.46.4.490Kim 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.2016.46.4.490Galiuto 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.2007.09.051Galiuto 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.2007.09.051Klug 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: 10.1186/1532-429X14-46Klug 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: 10.1186/1532-429X14-46Kitabata 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.2013.05.014Kitabata 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.2013.05.014Khorramirouz 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.2018.08.020Khorramirouz 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.2018.08.020Marcos-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.2021.11.050Marcos-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.2021.11.050Pezel 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.2020.05.024Pezel 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.2020.05.024Reindl 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/oeab033Reindl 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/oeab033Russo 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/zuaa004Russo 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/zuaa004Zhang 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.2021.804020Zhang 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.2021.804020Porto 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/ehs065Porto 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/ehs065McCartney 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.2018.19802McCartney 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.2018.19802Jesel 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.2006.10.022Jesel 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.2006.10.022Bloom 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/zuab032Bloom 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/zuab032Zalewski 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.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.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.113.001197Basili 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.113.001197Aitmokhtar 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.2016.12.017Aitmokhtar 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.2016.12.017Lee 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-131692Lee 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-131692Fracassi 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.0000000000000661Fracassi 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.0000000000000661Ghaleh 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.xGhaleh 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.xAbebe 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.H2018Abebe 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.H2018Toda 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.H678Toda 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.H678Abdelaziz 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.0000000000000423Abdelaziz 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.0000000000000423Piana 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.89.6.2514Piana 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.89.6.2514Wang 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.20149Wang 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.20149Nazir 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/ehw136Nazir 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/ehw136Niccoli 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.2013.02.009Niccoli 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.2013.02.009Taylor 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.2004.03.018Taylor 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.2004.03.018Eitel 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.2010.02.019Eitel 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.2010.02.019Tan 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.2018.01281Tan 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.2018.01281Clarke 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)90483-1Clarke 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)90483-1Herring 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/ehz115Herring 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/ehz115Gutstein 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)90258-9Gutstein 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)90258-9Sellke 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.2018.05.090Sellke 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.2018.05.090Aksu 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/s12872-015-0004-6Aksu 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/s12872-015-0004-6Navarese 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.29113Navarese 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.29113Darwish 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: 10.5144/0256-4947.2022.75Darwish 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: 10.5144/0256-4947.2022.75Zhao 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.2006.03.017Zhao 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.2006.03.017Ito 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)00604-4Ito 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)00604-4Bolognese 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.A7Bolognese 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.A7Chen 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.27047Chen 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.27047Tiller 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/zuab110Tiller 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/zuab110Dregoesc 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.14371Dregoesc 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.14371Tsujioka 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-09-1045Tsujioka 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-09-1045Shetelig 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.2018.04.053Shetelig 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.2018.04.053Ota 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.2014.10.013Ota 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.2014.10.013Beijnink 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.2021204265Beijnink 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.2021204265Fernández-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.117.310901Fernández-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.117.310901Bonfig 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.00347.2022Bonfig 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.00347.2022Bochaton 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.0245684Bochaton 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.0245684Xu 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.2019.0853Xu 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.2019.0853Ibanez 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.2019.05.024Ibanez 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.2019.05.024Massalha 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.121.020973Massalha 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.121.020973Khan 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.116.003403Khan 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.116.003403Naghshtabrizi 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.0000000000000863Naghshtabrizi 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.0000000000000863Aetesam-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.120.019899Aetesam-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.120.019899Knabb 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.53.1.33Knabb 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.53.1.33Buffington 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.48.3.416Buffington 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.48.3.416Golino 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.75.1.292Golino 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.75.1.292Fu 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/s12013-013-9581-0Fu 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

The authors declare that there are no conflicts of interest present.