Микроваскулярные повреждения и внутримиокардиальные кровоизлияния при ишемии/реперфузии сердца. Анализ клинических и экспериментальных данных

Острый инфаркт миокарда (ОИМ) до сих пор остается одной из основных причин смертности трудоспособного населения. В его развитии существенную роль играют такие патофизиологические изменения как микроваскулярная обструкция (МВО), микроваскулярное повреждение сердца (МПС) и внутримиокардиальные кровоизлияния (ВМК). ВМК ассоциированы с увеличением размера инфаркта и сократительной дисфункцией. ВМК предшествуют возникновению неблагоприятного ремоделирования сердца и сопровождаются воспалением. Экспериментальные исследования показывают, что ВМК происходят после реканализации инфаркт-связанной коронарной артерии, и их размер зависит от продолжительности ишемии. ВМК сопровождаются сократительной дисфункцией и неблагоприятным ремоделированием сердца. Наиболее вероятной причиной ВМК является МПС. МПС сопровождается увеличением уровня провоспалительных цитокинов в миокарде и плазме крови, а также снижением содержания белков плотных контактов в эндотелиальных клетках коронарных сосудов. Однако нет убедительных доказательств того, что провоспалительные цитокины вызывают МПС. Увеличение уровня провоспалительных цитокинов и МПС может быть двумя независимыми процессами. В этом обзоре мы анализируем клинико-экспериментальные данные о внутримиокардиальных кровоизлияниях и микрокроваскулярных повреждениях сердца при ишемии/реперфузии сердца.

1. Currey EM, Falconer N, Isoardi KZ, Barras M. Impact of pharmacists during in-hospital resuscitation or medical emergency response events: A systematic review. Am J Emerg Med. 2024;75:98-110. https://doi.org/10.1016/j.ajem.2023.10.020.

2. Ashraf S, Farooq U, Shahbaz A, et al. Factors Responsible for Worse Outcomes in STEMI Patients With Early vs Delayed Treatment Presenting in a Tertiary Care Center in a Third World Country. Curr Probl Cardiol. 2024;49:102049. https://doi.org/10.1016/j.cpcardiol.2023.102049.

3. Vyshlov EV, Alexeeva YA, Ussov WY, et al. Phenomena of microvascular myocardial injury in patients with primary ST-segment elevation myocardial infarction: Prevalence and association with clinical characteristics. The Siberian Journal of Clinical and Experimental Medicine. 2022;37:36-46. https://doi.org/10.29001/2073-8552-2021-36-4-36-46.

4. Maslov LN, Naryzhnaya NV, Popov SV, et al. A historical literature review of coronary microvascular obstruction and intra-myocardial hemorrhage as functional/structural phenomena. J Biomed Res. 2023;37:281-302. https://doi.org/10.7555/JBR.37.20230021.

5. Panteleev OO, Ryabov VV. Cardiogenic shock: What’s new? The Siberian Journal of Clinical and Experimental Medicine. 2022;36:45-51. https://doi.org/10.29001/2073-8552-2021-36-4-45-51.

6. Хубулава Г. Г., Козлов К. Л., Шишкевич А. Н., и др. Предикторы реперфузионного синдрома миокарда: современный взгляд на вопрос и актуальные проблемы. Часть 2: феномен невосстановленного коронарного кровотока, или феномен no-reflow (обзор литературы) // Регионарное кровообращение и микроциркуляция. 2021. Т. 20. С. 4–10. https://doi.org/10.24884/1682-6655-2021-20-3-4-10.

7. Ota S, Nishiguchi T, Taruya A, et al. Hyperglycemia and intramyocardial hemorrhage in patients with ST-segment elevation myocardial infarction. J Cardiol. 2022;80:456-61. https://doi.org/10.1016/j.jjcc.2022.06.003.

8. Ferré-Vallverdú M, Sánchez-Lacuesta E, Plaza-López D, et al. Prognostic value and clinical predictors of intramyocardial hemorrhage measured by CMR T2* sequences in STEMI. Int J Cardiovasc Imaging. 2021;37:1735-44. https://doi.org/10.1007/s10554-020-02142-7.

9. Rossington JA, Sol E, Masoura K, et al. 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:e001215. https://doi.org/10.1136/openhrt-2019-001215.

10. Maznyczka AM, McCartney P, Duklas P, et al. Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial. Heart. 2021:heartjnl-2020-317828. https://doi.org/10.1136/heartjnl-2020-317828.

11. Maznyczka AM, McCartney PJ, Oldroyd KG, et al. Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction. J Am Heart Assoc. 2020;9:e014066. https://doi.org/10.1161/JAHA.119.014066.

12. Bonfig NL, Soukup CR, Shah AA, et al. Circadian dependence of microvascular obstruction during ST-segment elevation myocardial infarction. Int J Cardiol. 2022;366:25-9. https://doi.org/10.1016/j.ijcard.2022.07.012.

13. Holzknecht M, Tiller C, Reindl M, et al. C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction. Int J Cardiol. 2021;338:30-6. https://doi.org/10.1016/j.ijcard.2021.06.023.

14. Ma M, Diao K-Y, Yang Z-G, et al. 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:e11617. https://doi.org/10.1097/MD.0000000000011617.

15. Tarantini G, Razzolini R, Cacciavillani L, et al. Influence of transmurality, infarct size, and severe microvascular obstruction on left ventricular remodeling and function after primary coronary angioplasty. Am J Cardiol. 2006;98:1033- 40. https://doi.org/10.1016/j.amjcard.2006.05.022.

16. Beek AM, Nijveldt R, van Rossum AC. Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2010;26:49-55. https://doi.org/10.1007/s10554-009-9499-1.

17. Ding S, Li Z, Ge H, Qiao Z-Q, Chen Y-L, Andong A-L, et al. Impact of Early ST-Segment Changes on Cardiac Magnetic Resonance-Verified Intramyocardial Haemorrhage and Microvascular Obstruction in ST-Elevation Myocardial Infarction Patients. Medicine (Baltimore). 2015;94:e1438. https://doi.org/10.1097/MD.0000000000001438.

18. Carrick D, Haig C, Ahmed N, et al. Myocardial Hemorrhage After Acute Reperfused ST-Segment-Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognostic Significance. Circ Cardiovasc Imaging. 2016;9:e004148. https://doi.org/10.1161/CIRCIMAGING.115.004148.

19. Alekseeva YV, Vyshlov EV, Pavlyukova EN, et al. Impact of microvascular injury various types on function of left ventricular in patients with primary myocardial infarction with ST segment elevation. Kardiologiia. 2021;61:23-31. https://doi.org/10.18087/cardio.2021.5.n1500.

20. Amier RP, Tijssen RYG, Teunissen PFA, et al. Predictors of Intramyocardial Hemorrhage After Reperfused ST-Segment Elevation Myocardial Infarction. J Am Heart Assoc. 2017;6:e005651. https://doi.org/10.1161/JAHA.117.005651.

21. Reinstadler SJ, Stiermaier T, Reindl M, et al. Intramyocardial haemorrhage and prognosis after ST-elevation myocardial infarction. Eur Heart J Cardiovasc Imaging. 2019; 20:138-46. https://doi.org/10.1093/ehjci/jey101.

22. Maznyczka AM, Carrick D, Carberry J, et al. Sexbased associations with microvascular injury and outcomes after ST-segment elevation myocardial infarction. Open Heart. 2019;6:e000979. https://doi.org/10.1136/openhrt-2018-000979.

23. Masci P-G, Pavon AG, Muller O, et al. Relationship between CMR-derived parameters of ischemia/reperfusion injury and the timing of CMR after reperfused ST-segment elevation myocardial infarction. J Cardiovasc Magn Reson. 2018;20:50. https://doi.org/10.1186/s12968-018-0474-7.

24. Yew SN, Carrick D, Corcoran D, et al. Coronary Thermodilution Waveforms After Acute Reperfused ST-Segment-Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognosis. J Am Heart Assoc. 2018;7:e008957. https://doi.org/10.1161/JAHA.118.008957.

25. Lim K, Yang JH, Hahn J-Y, et al. Impact of Natural Mild Hypothermia in the Early Phase of ST-Elevation Myocardial Infarction: Cardiac Magnetic Resonance Imaging Study. J Cardiovasc Imaging. 2018;26:175-85. https://doi.org/10.4250/jcvi.2018.26.e21.

26. Haig C, Carrick D, Carberry J, et al. Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights. JACC Cardiovasc Imaging. 2019;12:993-1003. https://doi.org/10.1016/j.jcmg.2018.05.022.

27. Podlesnikar T, Pizarro G, Fernández-Jiménez R, et al. Left ventricular functional recovery of infarcted and remote myocardium after ST-segment elevation myocardial infarction (METOCARD-CNIC randomized clinical trial substudy). J Cardiovasc Magn Reson. 2020;22:44. https://doi.org/10.1186/s12968-020-00638-8.

28. Lechner I, Reindl M, Tiller C, et al. Temporal Trends in Infarct Severity Outcomes in ST-Segment-Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study. J Am Heart Assoc. 2023;12:e028932. https://doi.org/10.1161/JAHA.122.028932.

29. Lechner I, Reindl M, Stiermaier T, et al. Clinical Outcomes Associated With Various Microvascular Injury Patterns Identified by CMR After STEMI. J Am Coll Cardiol. 2024;83:2052-62. https://doi.org/10.1016/j.jacc.2024.03.408.

30. Bulluck H, Rosmini S, Abdel-Gadir A, et al. Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-SegmentElevation Myocardial Infarction and Adverse Left Ventricular Remodeling. Circ Cardiovasc Imaging. 2016;9:e004940. https://doi.org/10.1161/CIRCIMAGING.116.004940.

31. Bodi V, Gavara J, Lopez-Lereu MP, et al. Impact of Persistent Microvascular Obstruction Late After STEMI on Adverse LV Remodeling: A CMR Study. JACC Cardiovasc Imaging. 2023;16:919-30. https://doi.org/10.1016/j.jcmg.2023.01.021.

32. Troger F, Pamminger M, Poskaite P, et al. Clinical Impact of Persistent Microvascular Obstruction in CMR After Reperfused STEMI. Circ Cardiovasc Imaging. 2025:e017645. https://doi.org/10.1161/CIRCIMAGING.124.017645.

33. Bochaton T, Lassus J, Paccalet A, et al. Association of myocardial hemorrhage and persistent microvascular obstruction with circulating inflammatory biomarkers in STEMI patients. PLoS One. 2021;16:e0245684. https://doi.org/10.1371/journal.pone.0245684.

34. Tiller C, Reindl M, Holzknecht M, et al. 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;11:113-23. https://doi.org/10.1093/ehjacc/zuab110.

35. Fukuyama T, Sobel BE, Roberts R. Microvascular deterioration: implications for reperfusion. Cardiovasc Res. 1984; 18:310-20. https://doi.org/10.1093/cvr/18.5.310.

36. Robbers LFHJ, Eerenberg ES, Teunissen PFA, et al. Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage. Eur Heart J. 2013;34:2346-53. https://doi.org/10.1093/eurheartj/eht100.

37. Chen W, Zhang B, Xia R, et al. T2 mapping at 7T MRI can quantitatively assess intramyocardial hemorrhage in rats with acute reperfused myocardial infarction in vivo. J Magn Reson Imaging. 2016;44:194-203. https://doi.org/10.1002/jmri.25145.

38. Hansen ESS, Pedersen SF, Pedersen SB, et al. Cardiovascular MR T2-STIR imaging does not discriminate between intramyocardial haemorrhage and microvascular obstruction during the subacute phase of a reperfused myocardial infarction. Open Heart. 2016;3:e000346. https://doi.org/10.1136/openhrt-2015-000346.

39. Nair AR, Johnson EA, Yang H-J, et al. Reperfused hemorrhagic myocardial infarction in rats. PLoS One. 2020;15:e0243207. https://doi.org/10.1371/journal.pone.0243207.

40. Assimopoulos S, Shie N, Ramanan V, et al. Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1, T2 and BOLD study. NMR Biomed. 2021;34:e4404. https://doi.org/10.1002/nbm.4404.

41. Ghugre NR, Pop M, Thomas R, et al. Hemorrhage promotes inflammation and myocardial damage following acute myocardial infarction: insights from a novel preclinical model and cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2017;19:50. https://doi.org/10.1186/s12968-017-0361-7.

42. Xia R, Zhu T, Zhang Y, et al. Myocardial infarction size as an independent predictor of intramyocardial haemorrhage in acute reperfused myocardial ischaemic rats. Eur J Med Res. 2022;27:220. https://doi.org/10.1186/s40001-022-00834-5.

43. Ritman EL. Computed tomography evaluation of regional increases in microvascular permeability after reperfusion of locally ischemic myocardium in intact pigs. Acad Radiol. 1995;2:952–8. https://doi.org/10.1016/s1076-6332(05)80694-4.

44. Platts SH, Linden J, Duling BR. Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation. Am J Physiol Heart Circ Physiol. 2003;284:H2360-2367. https://doi.org/10.1152/ajpheart.00899.2002.

45. Hollander MR, de Waard GA, Konijnenberg LSF, et al. Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction. PLoS One. 2016;11:e0157233. https://doi.org/10.1371/journal.pone.0157233.

46. Liu Y, Hu Y, Xiong J, Zeng X. Overexpression of Activating Transcription Factor 3 Alleviates Cardiac Microvascular Ischemia/Reperfusion Injury in Rats. Front Pharmacol. 2021;12:598959. https://doi.org/10.3389/fphar.2021.598959.

47. Gao X-M, Su Y, Moore S, et al. Relaxin mitigates microvascular damage and inflammation following cardiac ischemia-reperfusion. Basic Res Cardiol. 2019;114:30. https://doi.org/10.1007/s00395-019-0739-9.

48. Maslov LN, Popov SV, Mukhomedzyanov AV, et al. Reperfusion Cardiac Injury: Receptors and the Signaling Mechanisms. Curr Cardiol Rev. 2022;18:63-79. https://doi.org/10.2174/1573403X18666220413121730.