The general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease

Author:

Khokhlov A. L.1ORCID,Romashchenko O. V.2ORCID,Rumbesht V. V.3ORCID,Alferov P. K.3ORCID,Grishchenko N. D.3ORCID,Gorbach T. V.4ORCID,Kukes V. G.5ORCID

Affiliation:

1. Yaroslavl State Medical University

2. Yaroslavl State Medical University; Belgorod State National Research University

3. Belgorod State National Research University

4. Kharkov National Medical University

5. First Moscow State Medical University named by I.I. Sechenov

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.

Publisher

Publishing House OKI

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