Endothelial functional activity, inflammation level in patients with arterial hypertension combined with chronic obstructive pulmonary disease during combination therapy with meldonium

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Combination of arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular risk due to the synergistic effects of the inflammatory components of respiratory hypoxia, which affects the degree of arterial endothelial damage and the nature of proatherogenic vascular wall remodeling.

The aim: to estimate C-reactive protein (CRP) levels, condition of the intima-media complex (IMC), and endothelial functional activity in patients with AH and COPD receiving combination therapy including meldonium.

Material and methods. The study included 88 patients aged 35–67 years (mean age 48.3 ± 5.1 years) with stage 2 AH and myocardial ischemia during intense physical exertion. 44 participants had arterial hypertension in combination with moderate to severe COPD. Depending on the presence of COPD and treatment composition, all patients were randomized into four groups of 22 persons: Group 1 – patients with AH who received only traditional therapy (antihypertensive, lipid-lowering drugs); Group 2 – patients with AH + COPD only on traditional therapy; Group 3 – patients with AH who received meldonium in addition to traditional therapy; Group 4 – patients with AH + COPD who used meldonium in addition to traditional therapy. Patients with COPD also received the necessary bronchodilator therapy. At inclusion in the study and after 6 months of treatment, the level of CRP, thickness of the common carotid artery IMC, endothelium-dependent vasodilation of the brachial artery (EDVD) in the cuff test and mean pulmonary artery pressure were evaluated.

Results. Patients with combination of arterial hypertension and COPD showed more pronounced changes in the brachial artery EDVD. Administration of meldonium in complex therapy for patients with arterial hypertension and COPD was associated with a more pronounced reduction in CRP levels and IMC thickness, an improvement in EDVD, and a decrease in mean pulmonary artery pressure comparatively to treatment without this medicine.

Conclusion. Obtained data indicate the feasibility of using meldonium in patients with high cardiovascular risk and COPD, as it reduces the degree of vascular wall remodeling and impairment of vascular endothelial function.

全文:

受限制的访问

作者简介

Vadim Mikhin

Kursk State Medical University of the Ministry of Healthcare of Russia

编辑信件的主要联系方式.
Email: mikhinvp@kursksmu.net
ORCID iD: 0000-0002-5398-9727

MD, Dr. Sci. (Medicine), professor, head of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

Elena Khlebodarova

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: xlebodarovaev@kursksmu.net
ORCID iD: 0009-0006-4041-3848

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 1

俄罗斯联邦, Kursk

Fedor Khlebodarov

Kurchatov Central District Hospital

Email: rebus46@mail.ru
ORCID iD: 0009-0002-9298-1012

MD, Dr. Sci. (Medicine), chief physician

俄罗斯联邦, Kursk Region, Karl Liebknecht Settlement

Diana Vasilyeva

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: tbilisi2106@yandex.ru

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

Marina Chernyatina

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: mchernyatina@yandex.ru
ORCID iD: 0000-0002-0691-6357

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

Tamara Nikolenko

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: tomik7@yandex.ru
ORCID iD: 0000-0001-7987-9000

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

Nadezhda Kostina

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: costinanl@yandex.ru
ORCID iD: 0000-0002-2835-4762

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

Lina Maltseva

Kursk State Medical University of the Ministry of Healthcare of Russia

Email: lmal0785@rambler.ru
ORCID iD: 0009-0002-4467-371X

MD, PhD (Medicine), associate professor of the Department of internal medicine No. 2

俄罗斯联邦, Kursk

参考

  1. Григорьева Н.Ю. Коморбидный пациент с артериальной гипертонией и ХОБЛ. Лечащий врач.2016;(7):24. [Grigorieva NYu. Comorbid patient with arterial hypertension and COPD. Lechashchiy vrach = Attending physician. 2016;(7):24 (In Russ.)]. EDN: WMOCBN.
  2. Задионченко В.С., Адашева Т.В., Федорова И.В., Нестеренко О.И., Миронова М.А. Артериальная гипертония и хроническая обструктивная болезнь легких: клинико-патогенетические параллели и возможности терапии. Российский кардиологический журнал. 2009;14(6):62–69. [Zadionchenko VS, Adasheva TV, Fedorova IV, Nesterenko OI, Mironova MA. Arterial hypertension and chronic obstructive pulmonary disease: Clinico-pathogenetic parallels and therapeutic potential. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2009;14(6):62–69 (In Russ.)]. EDN: KZIRIB.
  3. Кароли Н.А., Ребров А.П. Хроническая обструктивная болезнь легких и кардиоваскулярная патология. Клиницист. 2007;(1):13–19. [Karoli NA, Rebrov AP. Chronic obstructive pulmonary disease and cardiovascular pathology. Klinitsist = The Clinician. 2007;(1):13–19 (In Russ.)]. EDN: MBDVWZ.
  4. Задионченко В.С., Адашева Т.В., Ли В.В., Жердева Е.И., Малиничева Ю.В., Нестеренко О.И., Павлов С.В. Артериальная гипертензия и хроническая обструктивная болезнь легких – проблемы выбора терапии. Лечащий врач. 2012;(7):77. [Zadionchenko VS, Adasheva TV, Li VV, Zherdeva EI, Malinicheva YuV, Nesterenko OI, Pavlov SV. Arterial hypertension and chronic obstructive pulmonary disease – problems of therapy choice. Lechashchiy vrach = Attending Physician. 2012;(7):77 (In Russ.)]. EDN: QKGCQZ.
  5. Chan P, Tomlinson B, Huang TY, Ko JT, Lin TS, Lee YS. Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough. J Clin Pharmacol. 1997;37(3):253–57. PMID: 9089428. https://doi.org/10.1002/j.1552-4604.1997.tb04788.x
  6. Myou S, Fujimura M, Kamio Y, Ishiura Y, Kurashima K, Tachibana H et al. Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma. Am J Respir Crit Care Med. 2000;162(1):40–44. PMID: 10903217. https://doi.org/10.1164/ajrccm.162.1.9907127
  7. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al.; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–87. PMID: 17563527. https://doi.org/10.1097/HJH.0b013e3281fc975a
  8. Чазова И.Е., Ратова Л.Г., Бойцов С.А., Небиеридзе Д.В., Карпов Ю.А., Белоусов Ю.Б. с соавт. Диагностика и лечение артериальной гипертензии (рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов). Системные гипертензии. 2010;(3):5–26. [Chazova IE, Ratova LG, Boytsov SA, Nebieridze DV, Karpov YuA, Belousov YuB et al. Diagnosis and treatment of arterial hypertension (recommendations of the Russian Medical Society on Arterial Hypertension and the All-Russian Scientific Society of Cardiologists). Sistemnyye gipertenzii = Systemic hypertension. 2010;(3):5–26 (In Russ.)] EDN: MXSHWH. https://doi.org/10.26442/SG28874
  9. Hunninghake DB. Cardiovascular disease in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):44–49. PMID: 16113468. https://doi.org/10.1513/pats.200410-050SF
  10. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343(4):269–80. PMID: 10911010. https://doi.org/10.1056/NEJM200007273430407
  11. Noguera A, Busquets X, Sauleda J, Villaverde JM, MacNee W, Agusti AG. Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1664–68. PMID: 9817722. https://doi.org/10.1164/ajrccm.158.5.9712092
  12. Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group. Am J Respir Crit Care Med. 1997;156(2 Pt 1):341–57. PMID: 9279209. https://doi.org/10.1164/ajrccm.156.2.9611013
  13. Домброва М., Дайя Д., Мипиньш Э., Кирьянова О., Калвиньш И. Биохимические механизмы действия Милдроната® в условиях ишемического стресса. Врачебное дело. 2004;(2):68–74. [Dombrova M, Daya D, Mipins E, Kiryanova O, Kalvins I. Biochemical mechanisms of Mildronate® action under conditions of ischemic stress. Vrachebnoe delo = Medical Business. 2004;(2):68–74 (In Russ.)].
  14. Калвиньш И.Я. Милдронат – механизм действия и перспективы его применения. Рига. 2002; 39 с. [Kalvins IYa. Mildronate – mechanism of action and prospects of its application. Riga. 2002; 39 pp. (In Russ.)].
  15. Михин В.П., Хлебодаров Ф.Е., Васильева Д.А., Громнацкий Н.И. Применение милдроната в комплексном лечении гипертонической болезни у пациентов с ишемической болезнью сердца и его влияние на морфофункциональное состояние сердца и сосудов. Consilium Medicum. 2019;21(12):68–73. [Mikhin VP, Khlebodarov FE, Vasilieva DA, Gromnatskii NI. Mildronate use in complex treatment of arterial hypertension in patients with ischemic heart disease and its influence on heart and vessels morphofunctional state. Consilium Medicum. 2019;21(12):68–73 (In Russ.)]. EDN: AEWKXG. https://doi.org/10.26442/20751753.2019.12.190699
  16. Akahira M, Hara A, Abiko Y. Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart. Fundam Clin Pharmacol. 1997;11(4):356–64. PMID: 9263766. https://doi.org/10.1111/j.1472-8206.1997.tb00849.x
  17. Liepinsh E, Vilskersts R, Loca D, Kirjanova O, Pugovichs O, Kalvinsh I, Dambrova M. Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. J Cardiovasc Pharmacol. 2006;48(6):314–19. PMID: 17204911. https://doi.org/10.1097/01.fjc.0000250077.07702.23
  18. Михин В.П. Цитопротекция в кардиологии: достигнутые успехи и перспективы. Часть 1. Архивъ внутренней медицины. 2014;(1):44–49. [Mikhin VP. Cytoprotection in cardiology: achievements and prospects. Part 1 Arkhiv vnutrenney meditsiny = Archive of Internal Medicine. 2014;(1):44–49 (In Russ.)]. EDN: TBCLLF.
  19. Михин В.П. Цитопротекция в кардиологии: достигнутые успехи и перспективы. Часть 2. Архивъ внутренней медицины. Часть 2. Архивъ внутренней медицины. 2014;(2):33–41. [Mikhin VP. Cytoprotection in cardiology: Achievements and prospects. Part 2. Arkhiv vnutrenney meditsiny = Archive of Internal Medicine. 2014;(2):33–41 (In Russ.)]. EDN: TBEBUJ.
  20. Михин В.П. Кардиоцитопротекторы – новое направление клинической кардиологии. Архивъ внутренней медицины. 2011;(1):21–28. [Mikhin VP. Cardiocytoprotectors – a new direction of clinical cardiology. Arkhiv vnutrenney meditsiny = Archive of Internal Medicine. 2011;(1):21–28 (In Russ.)]. EDN: RPELQV.
  21. Клинические рекомендации. Артериальная гипертензия у взрослых. Общероссийская общественная организация «Российское кардиологическое общество», Общероссийская общественная организация «Российское научное медицинское общество терапевтов». Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 62_3. Доступ: https://cr.minzdrav.gov.ru/view-cr/62_3 (дата обращения – 21.10.2025). [Clinical guidelines. Arterial hypertension in adults. Russian Society of Cardiology, Russian Scientific Medical Society of Internal Medicine. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2024. ID: 62_3. URL: https://cr.minzdrav.gov.ru/view-cr/62_3 (date of access – 21.10.2025) (In Russ.)].
  22. Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874–2071. PMID: 37345492. https://doi.org/10.1097/HJH.0000000000003480
  23. O’Donnell DE, Webb K, Neder JA. Lung hyperinflation in COPD: Applying physiology to clinical practice. COPD Res Pract. 2015;1(1):1–12. https://doi.org/10.1186/s40749-015-0008-8
  24. Галявич А.С., Терещенко С.Н., Ускач Т.М., Агеев Ф.Т., Аронов Д.М., Арутюнов Г.П. с соавт. Хроническая сердечная недостаточность. Клинические рекомендации 2024. Российский кардиологический журнал. 2024;29(11):251–349. [Galyavich AS, Tereshchenko SN, Uskach TM, Ageev FT, Aronov DM, Arutyunov GP et al. Chronic heart failure. Clinical guidelines 2024. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2024;29(11):251–349 (In Russ.)]. EDN: WKIDLJ. https://doi.org/10.15829/1560-4071-2024-6162
  25. Клинические рекомендации. Хроническая болезнь почек (ХБП). Национальная Ассоциация нефрологов. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 469_3. Доступ: https://cr.minzdrav.gov.ru/view-cr/469_3 (дата обращения – 21.10.2025). [Clinical guidelines. Chronic kidney disease (CKD). National Association of Nephrologists. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2024. ID: 469_3. URL: https://cr.minzdrav.gov.ru/view-cr/469_3 (date of access – 21.10.2025) (In Russ.)].
  26. Клинические рекомендации. Ожирение. Российская ассоциация эндокринологов, Общество бариатрических хирургов. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 28_3. Доступ: https://cr.minzdrav.gov.ru/view-cr/28_3 (дата обращения – 21.10.2025). [Clinical guidelines. Obesity. Russian Association of Endocrinologists, Society of Bariatric Surgeons. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2024. ID: 28_3. URL: https://cr.minzdrav.gov.ru/view-cr/28_3 (date of access – 21.10.2025) (In Russ.)].
  27. Ежов М.В., Кухарчук В.В., Сергиенко И.В., Алиева А.С., Анциферов М.Б., Аншелес А.А. с соавт. Нарушения липидного обмена. Клинические рекомендации 2023. Российский кардиологический журнал. 2023;28(5):250–297. [Ezhov MV, Kukharchuk VV, Sergienko IV, Alieva AS, Antsiferov MB, Ansheles AA et al. Disorders of lipid metabolism. Clinical guidelines 2023. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2023;28(5):250–297 (In Russ.)]. EDN: YVZOWJ. https://doi.org/10.15829/1560-4071-2023-5471
  28. Лелюк В.Г., Лелюк С.Э. Ультразвуковая ангиология. Монография. М.: Реальное время. 2003; 324 с. [Lelyuk VG, Lelyuk SE. Ultrasound angiology. Monograph. Moscow: Realnoe Vremya. 2003; 324 pp. (In Russ.)]. ISBN: 5-900080-20-X. EDN: QLELLB.
  29. Стародубова А.В., Кисляк О.А., Саргаева Д.С., Сторожаков Г.И., Сергиенко В.И., Говорун В.М., Джеджея Л.В. Оценка толщины интима-медиа у девушек-подростков и молодых женщин с ожирением и другими факторами риска сердечно–сосудистых заболеваний. Педиатрия. Журнал им. Г.Н. Сперанского. 2009;87(2):136–141. [Starodubova AV, Kislyak OA, Sargaeva DS, Storozhakov GI, Sergienko VI, Govorun VM, Dzhedzheya LV. Assessment of the thickness of inti-mate media in adolescent girls and young women with obesity and other risk factors for cardiovascular diseases. Pediatriya. Zhurnal imeni G.N. Speranskogo = Pediatrics. G.N. Speransky Journal. 2009;87(2):136–141 (In Russ.)]. EDN: KVKUUD.
  30. Яковлева О.И., Вахрамеева Н.В., Ларионова В.И., Богданова М.А., Конради А.О. Полиморфизм гена эндотелиальной NO-синтазы и структурно-функциональное состояние крупных сосудов у больных гипертонической болезнью с гипертрофией левого желудочка. Артериальная гипертензия. 2005;11(3):195–200. [Yakovleva OI, Vakhrameyeva NV, Larionova VI, Bogdanova MA, Konradi AO. The gene polymorphism of endothelial no-synthase and the structural and functional state of large vessels in hypertensive patients with left ventricular hypertrophy. Arterial’naya gipertenziya = Arterial Hypertension. 2005;11(3):195–200 (In Russ.)]. EDN: STXAJP.
  31. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: A direct measurement with ultrasound imaging. Circulation. 1986;74(6): 1399–406. PMID: 3536154. https://doi.org/10.1161/01.cir.74.6.1399
  32. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. 1992;340(8828):1111–15. PMID: 1359209. https://doi.org/10.1016/0140-6736(92)93147-f
  33. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, pro-motes atherosclerosis. Nat Med. 2013;19(5):576–85. PMID: 23563705. PMCID: PMC3650111. https://dx.doi.org/10.1038/nm.3145
  34. Хейло Т.С., Данилогорская Ю.А., Назаренко Г.Б., Мартынов А.И. Оценка влияния 6-недельной терапии мельдонием (Милдронат®) на показатели бульбарной капилляроскопии у пациентки с хронической ишемической болезнью сердца и головного мозга. Терапия. 2020;6(3):105–110. [Heylo TS, Danilogorskaya JuA, Nazarenko GB, Martynov AI. Estimation of the influence of 6 week therapy by meldonium (Mildronate®) at bulbar capillaroscopy indexes in chronic ischemic heart and brain disease female patient. Terapiya = Therapy. 2020;6(3):105–110 (In Russ.)].
  35. Полозова Э.И., Пузанова Е.В., Сеськина А.А. Взаимосвязь иммунологических нарушений, гипоксии и воспаления при артериальной гипертензии и метаболическом синдроме. Медицинская иммунология. 2020;22(5):1003–1008. [Polozova EI, Puzanova EV, Seskina AA. Relationship between immunological alterations, hypoxia and inflammation in arterial hypertension combined with metabolic syndrome. Meditsinskaya immunologiya = Medical Immunology (Russia). 2020;22(5):1003–1008 (In Russ.)]. EDN: NGLBGD. https://doi.org/10.15789/1563-0625-RBI-2059
  36. Chao J, Wood JG, Gonzalez NC. Alveolar hypoxia, alveolar macrophages, and systemic inflammation. Respir Res 2009;10(1):54. PMID: 19545431. PMCID: PMC2705912. https://doi.org/10.1186/1465-9921-10-54
  37. Недогода С.В. Мельдоний как наднозологический препарат. Consilium Medicum. 2020;22(5):57–61. [Nedogoda SV. Meldonium as a supernosological drug. Consilium Medicum. 2020;22(5):57–61 (In Russ.)]. EDN: LELZPK. https://doi.org/10.26442/20751753.2020.5.200208
  38. Шишкова В., Капустина Л. Рациональный подход к решению кардиометаболических проблем в терапии коморбидных пациентов. Врач. 2018;29(11):3–11. [Shishkova V, Kapustina L. A rational approach to solving cardiometabolic problems in the therapy of comorbid patients. Vrach = The Doctor. 2018;29(11):3–11 (In Russ.)]. EDN: YOUBTN. https://doi.org/10.29296/25877305-2018-11-01
  39. Стаценко М.Е., Лопушкова Ю.Е., Деревянченко М.В., Урлапова Е.И. Влияние мельдония на жесткость артерий и уровень С-реактивного белка в комплексной терапии хронической сердечной недостаточности и хронической обструктивной болезни легких. Терапия. 2020;6(5):94–101. [Statsenko ME, Lopushkova YuE, Derevyanchenko MV, Urlapova EI. The effect of meldonium on arterial stiffness and C-reactive protein levels in the complex therapy of chronic heart failure and chronic obstructive pulmonary disease. Terapiya = Therapy. 2020;6(5):94–101 (In Russ.)]. EDN: EFGEFI. https://dx.doi.org/10.18565/therapy.2020.5.94-101
  40. Михин В.П., Хлебодаров Ф.Е., Васильева Д.А., Стребкова Е.Д. Эффективность Милдроната у больных гипертонической болезнью с очень высоким сердечно-сосудистым риском на фоне терапии эналаприлом. Медицинский алфавит. 2018;1(4):7–11. [Mikhin VP, Khlebodarov FE, Vasilyeva DA, Strebkova ED. Efficacy of Mildronate in patients with hypertensive disease with very high cardiovascular risk during enalapril therapy. Meditsinskiy alfavit = Medical Alphabet. 2018;1(4):7–11 (In Russ.)]. EDN: OTXFAN.
  41. Корокин М.В., Артюшкова Е.В., Покровский M.В., Покровская Т.Г., Артюшкова Е.Б., Гладченко М.П. с соавт. Исследование эндотелио- и кардиопротективных свойств препарата «Кардионат» при моделировании L-Name-индуцированного дефицита оксида азота. Человек и его здоровье. 2007;(3):5–9. [Korokin MV, Artyushkova EV, Pokrovsky MV, Pokrovskaya TG, Artyushkova EB, Gladchenko MP et al. Investigating the endothelio-and cardioprotective effects of Kardionat in modelling the l-name-induced oxide nitrogen deficiency. Chelovek i yego zdorov’ye = Humans and Their Health. 2007;(3):5–9 (In Russ.)]. EDN: KCKSLX.
  42. Hilde JM, Skjorten I, Hansteen V, Melsom MN, Hisdal J, Humerfelt S, Steine K. Haemodynamic responses to exercise in patients with COPD. Eur Respir J. 2013;41(5):1031–41. PMID: 22903957. https://doi.org/10.1183/09031936.00085612
  43. Santos S, Peinado VI, Ramirez J, Melgosa T, Roca J, Rodriguez-Roisin R, Barbera JA. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J. 2002;19(4):632–38. PMID: 11998991. https://doi.org/10.1183/09031936.02.00245902
  44. Bunel V, Guyard A, Dauriat G, Danel C, Montani D, Gauvain C et al. Pulmonary arterial histologic lesions in patients with COPD with severe pulmonary hypertension. Chest. 2019;156(1):33–44. PMID: 30872017. https://doi.org/10.1016/j.chest.2019.02.333
  45. Syso JR, Machado RF. Classification and pathophysiology of pulmonary hypertension. Contin Cardiol Educ. 2018;4(1):2–12. https://doi.org/10.1002/cce2.71
  46. Михин В.П., Поздняков Ю.М., Хлебодаров Ф.Е., Кольцова О.Н. Милдронат в кардиологической практике – итоги, новые направления, перспективы. Кардиоваскулярная терапия и профилактика. 2012;11(1):96–103. [Mikhin VP, Pozdnyakov YuM, Khlebodarov FE, Koltsova ON. Mildronate in cardiology practice – current evidence, ongoing research, and future perspectives. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2012;11(1):96–103 (In Russ.)]. EDN: RCKGTF. https://doi.org/10.15829/1728-8800-2012-1-96-103
  47. Михин В.П., Хлебодаров Ф.Е. Перспективы применения Милдроната у больных с сердечно-сосудистой патологией. Российский кардиологический журнал. 2010;15(4):83–92. [Mikhin VP, Khlebodarov FE. Mildronate potential in patients with cardiovascular disease. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2010;15(4):83–92 (In Russ.)]. EDN: MUENKZ.

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Bionika Media, 2025