The general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease
A. L. Khokhlov,
O. V. Romashchenko,
V. V. Rumbesht,
P. K. Alferov,
N. D. Grishchenko,
T. V. Gorbach,
V. G. Kukes https://doi.org/10.37489/2949-1924-0019
Abstract
The purpose of the study: to develop a general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease (CHD). Materials and methods. Examination of 60 patients with CHD: stable angina pectoris of I-III functional classes was performed. According to the standard general clinical methods for verifying the diagnosis were used: ECG, Doppler echocardiography, coronary angiography, lipid profile, complete blood count, coagulogram, renal, hepatic complex. Also the condition of stress-realizing and stress-limiting systems of the functional system of adaptation was deeply examined in patients: determination of the level of personal anxiety by the method of questioning, determination of the concentration of cortisol, insulin, cAMP and cGMP in blood serum by the method of enzyme immunoassay; determination of the endothelial and inducible nitric oxide synthase levels in erythrocyte lysate by the method of enzyme immunoassay; the study of ATP and ADP concentrations in blood serum and erythrocytes, also the study of 2,3-DFG concentration in erythrocytes by spectrophotometric methods. The individual reactivity of blood leukocytes’ mitochondria of patients was estimated in vitro under the influence of metabolic drugs (trimetazidine, meldonium, cytoflavin) by confocal microscopy according to the technique developed and patented by us (mitochondria were stained with pyrene). The materials were processed statistically. Results. Two variants of the leukocyte mitochondrial response in patients with CHD to the introduction of metabolic correctors in vitro were found — in the form of their activation or inhibition, depending on numerous parameters of the initial state of patients, which served as the basis for the development of a general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease. According to this concept, the individual reactivity of a patient with CHD to the administration of a metabolic drug depends on the initial state of the functional adaptation system, which can be determined by the activity of stress-realizing and stress-limiting systems (cortisol/insulin ratio, serum cAMP/cGMP, eNOS, iNOS of erythrocyte lysate) and by the degree of preservation of the structure and function of effector organs. It is appropriate to prescribe drugs that stimulate energy metabolism in cells only to patients with initial hypoergosis, reduced mitochondrial activity at the phases of activation or resistance of the general adaptation syndrome, while maintaining reserves for energy adaptation, by short courses. Conclusion. A general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary artery disease has been developed, according to which metabolic correctors should be prescribed in short courses, provided that individual reserves for energy adaptation are preserved in patients with initial mitochondrial hypoergosis in the activation or resistance phase of the general adaptation syndrome.
About the Authors
A. L. Khokhlov
Yaroslavl State Medical University
Russian Federation
Competing Interests:
Russian Federation
Alexander L. Khokhlov — Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Rector and Head of the Pharmacology and Clinical Pharmacology Department, Chairman of the Ethics Council under the Ministry of Health of the Russian Federation
AuthorID: 467731
Yaroslavl
Competing Interests:
The authors declare no conflict of interest
O. V. Romashchenko
Yaroslavl State Medical University; Belgorod State National Research University
Russian Federation
Competing Interests:
Russian Federation
Olesya V. Romashchenko — Candidate of Medical Sciences, Associate Professor, Associate Professor of the Pharmacology and Clinical Pharmacology Department, Associate Professor of the Internal Diseases Propaedeutics Department of Medical Institute
AuthorID: 561440
Yaroslavl
Belgorod
Competing Interests:
The authors declare no conflict of interest
V. V. Rumbesht
Belgorod State National Research University
Russian Federation
Competing Interests:
Russian Federation
Vadim V. Rumbesht — Candidate of Technical Sciences, Associate Professor of the Mathematical and Software Information Systems Department of the Institute of Engineering and Digital Technologies
AuthorID: 423743
Belgorod
Competing Interests:
The authors declare no conflict of interest
P. K. Alferov
Belgorod State National Research University
Russian Federation
Competing Interests:
Russian Federation
Petr K. Alferov — Candidate of Medical Sciences, Associate Professor, Honored Doctor of the Russian Federation, Head of the Cardiology Department No. 1, Associate Professor of the Department of Hospital Therapy of the Medical Institute
Belgorod
Competing Interests:
The authors declare no conflict of interest
N. D. Grishchenko
Belgorod State National Research University
Russian Federation
Competing Interests:
Russian Federation
Natalya D. Grishchenko — Candidate of Medical Sciences, Associate Professor, Resident Physician of the Department of Cardiology No. 1, Associate Professor of the Department of Hospital Therapy of the Medical Institute
Belgorod
Competing Interests:
The authors declare no conflict of interest
T. V. Gorbach
Kharkov National Medical University
Ukraine
Competing Interests:
Ukraine
Tatyana V. Gorbach — Ph.D. in Biology, Associate Professor of the Department of Biochemistry
Kharkov
Competing Interests:
The authors declare no conflict of interest
V. G. Kukes
First Moscow State Medical University named by I.I. Sechenov
Russian Federation
Competing Interests:
Russian Federation
Vladimir G. Kukes — Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Honored Worker of Science of the Russian Federation, Honorary Head of the Department of Clinical Pharmacology and Internal Diseases Propaedeutics
AuthorID: 85590
Moscow
Competing Interests:
The authors declare no conflict of interest
References
1. Лупанов В. П. антиишемический метаболический модулятор триметазидин в лечении ишемической болезни сердца. Российский кардиологический журнал. 2017;(2):119-124. https://doi.org/10.15829/1560-4071-2017-2-119-124 [Lupanov V.P.antiischemic metabolic modulator trimetazidine in treatment of coronary heart disease. Russian Journal of Cardiology. 2017;(2):119-124. (In Russ.) https://doi.org/10.15829/1560-4071-2017-2-119-124]
2. Российское кардиологическое общество (РКО). Стабильная ишемическая болезнь сердца. Клинические рекомендации 2020. Российский кардиологический журнал. 2020;25(11):4076. https://doi.org/10.15829/29/1560-4071-2020-4076
3. Прокофьева А. А., Савельева В. В. Кардиоцитопротекторы как перспективное направление улучшения энергообеспеченности миокарда. Молодежь и наука: шаг к успеху. 2020;220-223.
4. Прокофьева А. А. Принципы включения кардиоцитопротекторов в стандартные схемы лечения заболеваний сердечно-сосудистой системы. Студенческий форум. 2021;32-1:33-34.
5. Филиппова А. В., Переверзев А. П., Эбзеева Е. Ю., Остроумова О. Д. Милдронат. Синдром хронической усталости. Медицинский алфавит. 2020;(7):15-20. https://doi.org/10.33667/2078-5631-2020-7-15-20 [Filippova A.V., Pereverzev A.P., Ebzeeva E.Yu., Ostroumova O.D. Mildronate. Chronic fatigue syndrome. Medical alphabet. 2020;(7):15-20. (In Russ.) https://doi.org/10.33667/2078-5631-2020-7-15-20]
6. Ромащенко О. В. Персонализированные подходы к назначению триметазидина в качестве цитопротектора у пациентов с ишемической болезнью сердца. Российский кардиологический журнал. 2021;26(6):4532. https://doi.org/10.15829/1560-4071-2021-4532 [Romashchenko O.V. Personalized trimetazidine prescription as a cytoprotective agent in patients with coronary artery disease. Russian Journal of Cardiology. 2021;26(6):4532. (In Russ.) https://doi.org/10.15829/1560-4071-2021-4532].
7. Ромащенко О. В. Возможность персонализированного использования цитофлавина в качестве цитопротектора при ишемической болезни сердца // Экспериментальная и клиническая фармакология. — 2021. — 84(10):19-24. https://doi.org/10.30906/0869-2092-2021-84-10-19-24
8. Romaschenko OV, Pokrovsky MV, Nadezhdin SV, et al. Personalized Approaches to the Use of the Antioxidant Ethoxidol in Patients with Coronary Heart Disease. J Nanostruct, 2022; 12(2):343-352. DOI: 10.22052/JNS.2022.02.011.
9. Romaschenko OV, Pokrovsky MV, Nadezhdin SV, et al. Personalized Approaches to the Use of the Antioxidant Ethoxidol in Patients with Coronary Heart Disease. J Nanostruct, 2022; 12(2):343-352. DOI: 10.22052/JNS.2022.02.011.
10. Ferrari R, Camici PG, Crea F, Danchin N, Fox K, Maggioni AP, Manolis AJ, Marzilli M, Rosano GMC, Lopez-Sendon JL. Expert consensus document: A 'diamond' approach to personalized treatment of angina. Nat Rev Cardiol. 2018 Feb;15(2):120-132. doi: 10.1038/nrcardio.2017.131. Epub 2017 Sep 7. PMID: 28880025.
11. Судаков К. В., Кукес В. Г., Хоманов К. Э., Жестовская А. С. Возможность восстановления функционального состояния адаптационных систем организма с применением методологии персонализированной медицины. Лекарственные препараты и рациональная фармакотерапия. 2013;2:3-5.
12. Виноградов В. В. Гормоны, адаптация и системные реакции организма. — Минск: Наука и техника, 1989. — 223с.
13. Гаркави Л. Х., Квакина Е. Б., Уколова М. А. Адаптационные реакции и резистентность организма. — Ростов-на-Дону: Изд-во Ростовского ун-та, 1977. — 120с.
14. Коркушко О. В. Сердечно-сосудистая система и возраст: (клинико-физиологические аспекты). — М.: Медицина, 1983. — 176с.
15. Малышев И. Ю., Манухина Е. Б. Стресс, адаптация и оксид азота. Биохимия. 1998;63(7):992-1006.
16. Манухина Е. Б., Малышев И. Ю. Стресс-лимитирующая система оксида азота. Российский физиологический журнал им. И.М. Сеченова. 2000;(86)10:1283-1292.
17. Меерсон Ф. З. Адаптация, стресс и профилактика. — М.: Наука, 1981. — 280с.
18. Меерсон Ф.З. Адаптация, деадаптация и недостаточность сердца. — М.: Медицина, 1978. — 344с.
19. Никонов В. В. Стресс: современный патофизиологический подход к лечению. — Харьков: Консум, 2002. — 240с.
20. Панин Л. Е. Энергетические аспекты адаптации. — Л.: Медицина, 1978. — 189с.
21. Пшенинникова М. Г. Феномен стресса. Эмоциональный стресс и его роль в патологии. Патологическая физиология и экспериментальная терапия. 2000;4:21-31.
22. Пшенинникова М. Г. Феномен стресса. Эмоциональный стресс и его роль в патологии (продолжение). Патологическая физиология и экспериментальная терапия. 2001;1:26-31.
23. Радченко О. М. Адаптацiйнi реакцii, iх значення у клiнiцi внутрiшнiх хвороб: автореф. дис. … д-ра мед. наук. Киев, 2004. — 30с.
24. Фролькис В. В. Стресс-возраст-синдром. Физиологический журнал. 1991;37(3):3-11.
25. Фурдуй Ф. И. Физиологические механизмы стресса и адаптации при остром действии стресс-факторов. Кишинев: Штиинца, 1986. — 240с.
26. Хайдарлиу С. Х. Нейромедиаторные механизмы адаптации. Кишинев: Штиинца, 1989. — 180с.
27. Swynghedauw B., Rappaport L., Schwartz K. Heart failure as a disease of adaptation. Cardiac hypertrophy and failure / ed. by B. Swynghedauw. — London ; Paris, 1990. — P. 679-686.
28. Хазанов В. А. Фармакологическая регуляция энергетического обмена. Экспериментальная и клиническая фармакология. 2009;72(4):61-64.
29. Лукьянова Л. Д., Дудченко А. М., Цыбина Т. А., Германова Э. Л. Регуляторная роль митохондриальной дисфункции при гипоксии и её взаимодействие с транскрипционной активностью. Вестник Российской АМН. 2007;2:3-13.
30. Ромащенко О. В. Патент РФ на изобретение №2578436 «Способ определения индивидуальной реактивности митохондрий человека под действием препаратов метаболического ряда в пробах in vitro» 25.02.2016.
31. Лапач С. Н., Чубенко А. В., Бабич П. Н. Статистические методы в медико-биологических исследованиях с использованием Excel. — 2-е изд., перераб. и доп. — Киев: Морион, 2001. — 408с.
32. Петри А., Сэбин К. Наглядная медицинская статистика. — 2-е изд., перераб. и доп. — М.: ГЭО-ТАР-Медиа, 2010. — 168с.
33. Селье Г. Очерки об адаптационном синдроме. — М.: Медгиз, 1960. — 254с.
34. Гейченко В. П., Курята А. В., Мужчиль (Ромащенко) О. В. Сердечная недостаточность. Механизмы развития, роль нарушений метаболизма и адаптации, стратегии лечения. — Днепропетровск: ЧП «Лира ЛТД», 2007. — 216с.
35. Ларина В. Н. Мультисистемный эффект цитопротекции. Consilium Medicum. 2021;23(1): 93–98. DOI: 10.26442/20751753.2021.1.200732
36. Tsibulnikov SY, Maslov LN, Gorbunov AS, Voronkov NS, Boshchenko AA, Popov SV, Prokudina ES, Singh N, Downey JM. A Review of Humoral Factors in Remote Preconditioning of the Heart. J Cardiovasc Pharmacol Ther. 2019 Sep;24(5):403-421. doi: 10.1177/1074248419841632. Epub 2019 Apr 29. PMID: 31035796.
37. de Paula LJC, Uchida AH, Rezende PC, Soares
38. P, Scudeler TL. Protective or Inhibitory Effect of Pharmacological Therapy on Cardiac Ischemic Preconditioning: A Literature Review. Curr Vasc Pharmacol. 2022;20(5):409-428. doi: 10.2174/15701 61120666220819163025. PMID: 35986546.
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For citations:
Khokhlov A.L., Romashchenko O.V., Rumbesht V.V., Alferov P.K., Grishchenko N.D., Gorbach T.V., Kukes V.G. The general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease. Patient-Oriented Medicine and Pharmacy. 2023;1(3):1-14. (In Russ.) https://doi.org/10.37489/2949-1924-0019
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