INTRODUCTION
Despite the obvious achievements of modern cardiology, high disability and mortality rates in the population due to complicated variants of the clinical course of coronary heart disease (CHD) still persist [Bockeria L.A. et al., 2002; Belenkov Yu.N., 2002; Charmadov M.V., 2010]. Ischemic cardiomyopathy (ICMP) occupies a special position in the general structure of coronary artery disease [Kuznetsov D.V., 2004]. The incidence of ICMP, according to different authors, ranges from 10 to 35% [Iskandrian A.S., 1992; Belenkov, Yu.N., 2002]. Despite the obvious progress in the therapeutic treatment of complicated forms of IHD, the annual mortality rate in the general population of patients with IHD and severe left ventricular (LV) dysfunction is more than 20% [Belenkov, Yu.N., 2002], and the prognosis for five-year survival does not exceed 50% [Schinkel A.
F., 2007; Wilson Tang W.H., 2010].
The accumulation of experience in the surgical treatment of patients with low myocardial contractility, the improvement of surgical and anesthesiological care, the widespread use of methods of intraoperative myocardial protection and circulatory support methods have made it possible to expand the indications and improve the results of cardiac surgery in people with ICMP.
The most common cause of unfavorable outcomes of surgical treatment of patients with complicated ischemic heart disease is associated with a high risk of developing perioperative complications, which occupy a leading place in the structure of causes of mortality and disability in people with ICMP in the early and late periods after cardiac surgery [AI-Ruzzeh S., 2001; Attaran S. et al., 2010; Tkachev, E.V., 2012].
The nature of preoperative preparation plays an important role in the development of postoperative complications in cardiac surgery patients. The current routine practice of preparing patients for surgical intervention, based solely on the medicinal principle, does not fully protect the patient from the stressors of surgical trauma [Makshanov I.Ya., 2002].
A promising direction in the modern system of preoperative preparation is an integrated approach with the additional use of technologies that increase the body’s compensatory and adaptive capabilities to multicomponent surgical stress in order to improve the tolerance of surgical trauma and prevent severe metabolic complications in the perioperative period.
The most preferred non-pharmacological method, which fully meets the objectives of preoperative preparation, is the method of intermittent normobaric hypoxic therapy (INH) [Shevchenko Yu.L. et al., 2000; Strelkov, R.B., 2001; Goranchuk V.V. et al., 2003].
This study is aimed at studying the effectiveness of the clinical application of the INH method in preoperative preparation for surgical stress to improve the results of cardiac surgical treatment of patients with ICMP.
GENERAL CHARACTERISTICS OF WORK
Connection of work with major scientific projects and topics
The work was carried out within the framework of research topic No. 301 “Develop and implement a method of complex therapy of chronic heart failure using hypoxic training in patients with coronary heart disease in preparation for coronary artery bypass surgery” (No. GR 20091431 dated 10.07.2009).
Purpose of the study
To modify the technique of intermittent normobaric hypoxic therapy and evaluate the effectiveness of its use in preoperative preparation for cardiac surgical treatment of patients with ischemic cardiomyopathy.
Research objectives
1. Conduct a comprehensive assessment of the factors that determine the severity of the clinical course of the underlying disease and the risk of developing perioperative complications in patients with ischemic cardiomyopathy.
2. To modify the technique of intermittent normobaric hypoxic therapy for preoperative preparation for cardiac surgical treatment of patients with ischemic cardiomyopathy.
3. To determine the effect of intermittent normobaric hypoxic therapy on the functional reserves of the cardiorespiratory system and the main parameters of the blood gas transport system, as well as on the state of perfusion and electrical stability of the myocardium in patients with ischemic cardiomyopathy in the preoperative period.
4. Conduct a comparative assessment of the clinical course of the perioperative period and its complications in early and long-term follow-up in a group of patients using standard preoperative preparation and in a group of patients with an additional course of INH.
5. Assess the cost-effectiveness of using the proposed method of preoperative preparation.
Provisions for defense
1. The modified method of intermittent normobaric hypoxic therapy is well tolerated, safe and effective in preoperative preparation for cardiac surgical treatment of patients with ischemic cardiomyopathy, including those with class III–IV CHF severity.
2. Intermittent normobaric hypoxic therapy in patients with ICMP has a stimulating effect on the functional parameters of the cardiorespiratory system and improves the functioning of the blood gas transport system, as well as increases the body’s adaptive reserves to hypoxia conditions and operational stress.
3. Intermittent normobaric hypoxia therapy in patients with ICMP improves perfusion and electrical stability of the hibernating myocardium.
4. An integrated approach to the preoperative preparation of patients with ICMP, including the additional use of intermittent normobaric hypoxic therapy, has a beneficial effect on the course of the perioperative period and improves the results of cardiac surgical treatment in people at high risk of developing postoperative complications.
Personal contribution of the applicant
The author of the dissertation collected clinical material, performed primary examination, treatment and follow-up of patients at the pre- and postoperative stage. The selection of special dosing regimens for hypoxic stimulation, development, implementation and conduct of a course of intermittent normobaric hypoxic therapy sessions was carried out with the direct participation of the applicant. She also carried out the analysis and interpretation of data from clinical and instrumental diagnostic methods, and performed statistical processing of the results obtained. The author’s personal participation in obtaining the scientific results presented in the dissertation is 75% and is confirmed by co-authorship in publications on the topic of the dissertation.
Approbation of the dissertation results
The materials and main results of the dissertation were reported and discussed at the congresses of the European Society of Heart Failure Specialists (Berlin, 2010; Gothenburg, 2011; Belgrade, 2012; Lisbon, 2013), the V and VI congresses of the Russian Society of Heart Failure Specialists (Moscow, 2010, 2011), the XIX Congress of the International Society of Holter Monitoring and Noninvasive Electrocardiology (Moscow, 2011), II Eurasian Congress of Cardiologists (Minsk, 2011), II and III International Congresses “Cardiology at the Crossroads of Sciences” (Tyumen, 2011, 2012), XVII All-Russian Congress of Cardiovascular Surgeons (Moscow, 2011), XIV Congress of the World Arrhythmia Society (Athens, 2011), VII International Scientific and Practical Conference “Endothelial Dysfunction” (Vitebsk, 2012), IV United Conference of Cardiothoracic Surgeons of Scandinavia (Vilnius, 2012), 31st International Symposium on Cardiovascular Surgery (Zurich, 2013), XX European Congress of Clinical Chemistry and Laboratory Medicine (Milan, 2013), 28th Meeting of the Association of Cardiac Surgeons (Madrid, 2013).
For the report containing the dissertation materials, presented at the competition of scientific works of young scientists, held within the framework of the V Congress of the Russian Society of Heart Failure Specialists “Heart Failure 2010”, the applicant was awarded the title of First Prize Laureate of the competition of young scientists.
Publication of the dissertation results
Based on the dissertation materials, 26 printed works were published, including 6 articles in peer-reviewed journals, 2 articles in collections of scientific papers, with a total volume of 7.43 author’s pages, 17 abstracts of reports in the materials of scientific congresses, congresses, conferences (Belarus, Russia, Sweden, Greece, Lithuania, Serbia, Germany, Austria, Italy, Portugal, Spain), 1 instruction for use “Method of using interval hypoxic training in patients with ischemic cardiomyopathy in preparation for coronary bypass surgery under artificial circulation” (Nº GR 202-1210 dated 08.04.2011).
A patent was received for the invention “Method of preparing a patient for cardiac surgery treatment” / T.A. Dubovik, L.V. Rachok; registration in the State Register of Inventions No. 18002 dated 11.11.2013
Structure and scope of the dissertation
The dissertation work is presented on 147 pages of text and consists of a list of symbols, an introduction, a general description of the work, six chapters outlining their own results, a conclusion, and a bibliography. The dissertation is illustrated with 18 tables and 10 figures. The bibliographic list includes 215 works (106 domestic authors and from the CIS countries, 109 foreign ones).
MAIN CONTENT
Material and research methods
An open prospective study was conducted involving 95 patients with ischemic cardiomyopathy and targeted selection for cardiac surgery. The diagnosis of ICMP was established on the basis of standardized diagnostic criteria: the presence of indications of a previous myocardial infarction; echocardiography parameters: left ventricular (LV) end-diastolic size greater than 57 mm, LV ejection fraction less than 35%, local contractility impairment index greater than 1.31, relative LV wall thickness index less than 0.45; diagnosed hemodynamically significant stenotic lesion of the coronary arteries; presence of symptoms of heart failure (NYHA FC I–IV).
Inclusion criteria for the study: patients with a verified diagnosis of ischemic cardiomyopathy, subject to surgical revascularization of the myocardium, provided there is a sufficient volume of viable myocardium (≥ 50% of myocardium with radiopharmaceutical accumulation greater than 50%); availability of informed consent to participate in the study.
Exclusion criteria: cardiomyopathy of non-ischemic origin; pathology of the valve apparatus of rheumatic etiology; right ventricular failure (RV ejection fraction less than 35%); pathology of the thyroid gland requiring drug correction; hemodynamically significant disturbances of blood flow in the extracranial region; diabetes mellitus in the stage of decompensation; primary or secondary erythrocytosis; individual intolerance to oxygen deficiency, determined by the results of an acute hypoxic test.
After verification of the diagnosis in a group of 25 patients with ICMP, the method of conducting a course of intermittent normobaric hypoxic therapy (INH) was previously modified and clinically tested. 70 patients were divided into two groups comparable in terms of main clinical, laboratory and instrumental parameters: 35 patients in the control group (CG) with standard preoperative preparation and 35 people in the main group (MG), who, against the background of standard drug preparation in the preoperative period, underwent a course of adaptive hypoxic therapy using a modified technique for conducting INH.
All patients in the MG and CG underwent a comprehensive clinical examination, including clinical and anamnestic data, a 6-minute walk test (6 MTX), and an assessment of the level of quality of life using the Minnesota Quality of Life Questionnaire for Patients with Chronic Heart Failure (MLHFQ). Instrumental diagnostics consisted of transthoracic echocardiography, single-photon emission computed tomography with 99mTc-MIBI, daily electrocardiogram monitoring, spiroveloergometry, and coronary angiography. Among the laboratory research methods, general clinical and biochemical blood tests were used, and the main parameters of the blood gas composition were assessed.
Instrumental and clinical laboratory studies were carried out in patients in the MG at baseline, at the end of the course of INH, as well as on the 1st and 10–14 days after cardiac surgery; in patients CG – at baseline, on the 1st and 10–14 days after surgery. The clinical effectiveness of cardiac surgical treatment of patients with ICMP was assessed in the early postoperative period using the following endpoints: postoperative mortality; the nature and frequency of development of perioperative complications (perioperative myocardial infarction (PIM); low cardiac output syndrome (LOCS), requiring the connection of intra-aortic balloon counterpulsation (IABP); life-threatening arrhythmias; non-cardiac complications; length of stay of patients in the ICU).
In the long-term postoperative period (after 1 year), mortality was taken into account; number of hospitalizations per year due to progression of CHF; primary access to disability and increasing the disability group.
Calculation of the economic efficiency of the proposed method of preoperative preparation was carried out by comparing the costs of treating patients in the MG and CG in the intra- and early postoperative period.
Statistical analysis
Statistical processing of the obtained results was carried out using the statistical program package “Statistica v. 7.0”. All variation series were tested for normality of variance distribution using the Kolmogorov-Smirnov method. Data are presented as the arithmetic mean ± standard error of the arithmetic mean (M ± m) in the case of a normal distribution of the trait or as the median (Me) and interquartile range (Lower Quartile (LQ) = 25th percentile; Upper Quartile (UQ) = 75th percentile) in the case of a non-normal distribution of the trait. The reliability of intergroup differences in mean values on a quantitative basis was studied using Student’s t-test for dependent and independent samples with a normal distribution, and with a non-normal distribution – non-parametric Mann-Whitney U test for unrelated groups and Wilcoxon paired comparison test for related groups.
Characterization of differences in qualitative traits was carried out by assessing the frequency of the studied trait based on Fisher’s exact test or χ²-Pearson for data from 2×2 tables in two independent samples and using the McNemar test between dependent samples. The difference was considered statistically significant at a probability level of 95% (p less than 0.05).
Research results and discussion
Modification of the methodology for conducting a course of INH in preoperative preparation for cardiac surgical treatment of patients with ICMP
The course of adaptation hypoxic therapy in complex preoperative preparation for cardiac surgical treatment of patients with ICMP included 10 daily 50-minute INH sessions on the Bio-Nova-204 G1 device (Russia) using a gentle mode of stepwise adaptation to hypoxia. Each session consisted of five repeated 10-minute cycles. In each cycle, 5-minute intervals of exposure to a hypoxic gas mixture (HGM) alternated with 5-minute intervals of breathing atmospheric air. In the modified technique, during the first INH session, HGM with a high oxygen content was used (11% instead of 10%), and the maximum permissible exposure to continuous hypoxic exposure in one cycle was reduced from 5 to 3 minutes, which was supplied intermittently, by alternating 1-minute intervals of exposure to HGM and 1-minute intervals of breathing atmospheric air; Subsequently, the duration of continuous hypoxic exposure was increased stepwise from session to session and the time intervals of hypoxic stimulation and atmospheric air breathing were changed.
Modified methodology for conducting a course of INH for people with ICMP: • 1st session includes five cycles, during each of which, during the first, third and fifth minutes, breathing is carried out with a hypoxic gas mixture with 11% oxygen content, during the second, fourth and sixth-tenth minutes – with atmospheric air. The total hypoxic effect per session is 15 minutes; • The 2nd session includes five cycles, during each of which, during the first, second and fifth minutes, breathing is carried out with a hypoxic gas mixture with 10% oxygen content, and during the third, fourth and sixth-tenth minutes – with atmospheric air.
The total hypoxic effect per session is 15 minutes; • 3rd session includes five cycles, during each of which hypoxic breathing is carried out during the first, second, fourth and fifth minutes gas mixture with 10% oxygen content, during the third and sixth to tenth minutes – with atmospheric air. The total hypoxic effect per session is 20 minutes; • Sessions 4-10 include five cycles, during each of which a hypoxic gas mixture with 10% oxygen is breathed for five minutes and atmospheric air is breathed for five minutes. The total hypoxic effect is 25 minutes.
The modified INH technique made it possible to achieve good tolerability and complete safety of use in people with ICMP.
Assessment of the initial status of patients with ICMP in the comparison groups
According to the main clinical and laboratory-instrumental characteristics, as well as the drug treatment administered, the patients in the comparison groups did not differ significantly at baseline (Table 1).
The severity of the condition of all studied patients with ICMP in the comparison groups was associated with the presence of unfavorable structural, geometric and functional changes in the heart due to the maladaptive nature of LV cavity remodeling against the background of multivessel coronary artery disease and was characterized by a pronounced decrease in LVEF (LVEF less than 30%) with an increase in the size and volume of the LV, as well as changes in the shape and thickness of the LV walls (Table 1).
The severity of morphofunctional changes in the heart in people with ICMP was also determined by significant disturbances in myocardial perfusion without significant differences between the comparison groups. Based on the results of SPECT with 99mTc-MIBI, the following initial data were obtained: the volume of the myocardium with normal perfusion was 52.94 (35.29; 61.53)% in the MG and 46.15 (35.29; 52.94)% in the CG (p=0.245), the percentage of the myocardium with moderate and severe perfusion defects was – 35.29 (23.53; 41.18)% and 11.77 (0.00; 23.08)% in the MG with 41.18 (30.77; 46.15)% and 7.69 (0.00; 17.65)% in the CG, respectively (p more than 0.05).
The area of viable myocardium was 84.62 (76.47; 99.82)% in the MG and 84.62 (76.92; 100.00)% in the CG (p=0.601).
Patients in both comparison groups were characterized by the presence of unfavorable ectopic myocardial activity as another manifestation of ischemic cardiac remodeling and the severity of the underlying pathological process in individuals with ICMP (Table 2).
The influence of intermittent normobaric hypoxic therapy on the main parameters of the blood gas transport system
The oxygen transport function of blood and the adequacy of O₂ consumption by body tissues during adaptation to hypoxia were studied by the dynamics of parameters of the gas composition of venous blood before and after a course of INH (Table 3).
One of the effects of adaptation to intermittent hypoxia in patients with ICMP was an increase in the oxygen capacity of the blood during the course of INH due to an increase in the number of red blood cells and stimulation of hemoglobin synthesis, which had a beneficial effect on the oxygen transport properties of the blood and a decrease in the severity of metabolic acidosis and hypoxemia and was confirmed by a significant increase in the level of pH and HCO₃⁻, an increase in the concentration of buffer bases in the blood and the concentration of O₂ associated with hemoglobin and dissolved in blood plasma (ctO₂), degree of hemoglobin oxygen saturation (sO₂), degree of blood oxygen saturation (SpO₂) (Table 3).
One of the significant effects of adaptation to O₂ deficiency in individuals with ICMP was a significant increase in partial blood oxygen tension (pO₂) after a course of INH (Table 3). According to research by Swift P.C. et al. (1992), an increase in blood pO₂ helps restore the function of hibernating myocardiocytes in ischemic tissues, which plays a significant role in the preoperative preparation of patients with ICMP.
The influence of intermittent normobaric hypoxic therapy on the general functional state of the body
After a course of exposure to INH in patients with ICMP, there was an improvement in the clinical course of CHF and an increase in tolerance to physical activity, which was reflected in a significant increase in the level of VO₂max and VO₂max% of the expected (Table 4), as well as a decrease in the severity marker of CHF BNP from 310.20 (174.23; 668.01) to 180.49 (86.92; 335.79) pg/ml (p=0.000).
The beneficial effect of adaptive hypoxic therapy on the general functional state of the body and the activation of compensatory-adaptive reserves of patients with ICMP was confirmed by a significant increase in the load according to spiroveloerogometry of the volume of work performed by the subjects, an increase in the power of the threshold load, as well as an increase in the absolute value of the double product index and the magnitude of its increase (Table 4).
The safety of the proposed hypoxic stimulation regimen in individuals with ICMP was confirmed by the absence of negative changes in pulmonary ventilation parameters (minute volume of respiration (VE), ventilation equivalents for both O₂ (VE/VO₂) and CO₂ (VE/VCO₂), as well as the “dead space” / tidal volume (VD/VT) ratio) in the subjects studied against the background of adaptation to oxygen deficiency (Table 4).
The influence of intermittent normobaric hypoxic therapy on the state of perfusion and electrical stability of the myocardium
The effective influence of INH on the functional reserves of the blood gas transport system and the reserve compensatory and adaptive capabilities of the body had a beneficial effect on the state of perfusion of viable areas of the myocardium, which was confirmed by a significant increase in the area of viable myocardium after a course of INH from 84.62 (76.47; 99.82)% to 94.12 (92.31; 100.00)% (p=0.000), reducing the total number of segments with impaired perfusion from 7.57±0.53 to 5.89±0.43 (p=0.002), while the number of segments with normal perfusion increased from 7.57±0.44 to 8.60±0.51 (p=0.029), and the number of segments with severe hypoperfusion decreased with 2.09±0.33 to 0.86±0.20 (p=0.000).
After a course of exposure to INH, the volume of myocardium with normal perfusion increased significantly from 52.94 (35.29; 61.53)% to 58.82 (46.15; 76.47)% (p=0.015) with statistical a significant decrease in the volume of myocardium with pronounced perfusion defects from 11.77 (0.00; 23.08)% to 5.88 (0.00; 7.69)% (p=0.001).
The results obtained made it possible to confirm the assumption of the effective influence of adaptive hypoxic therapy on chronic reversible ischemic dysfunction and myocardial hypoperfusion that occurs against the background of a sustained decrease in coronary blood flow with occlusive lesions of the coronary arteries, which also had a beneficial effect on reducing the prognostically unfavorable ectopic activity and increasing the electrical stability of the myocardium after a course of INH (Table 5), which undoubtedly plays an important role role in the preoperative preparation of this category of patients.
Comparative assessment of the effectiveness of cardiac surgical treatment in the study comparison groups of patients with ICMP
After preoperative preparation, all patients underwent surgical revascularization of the myocardium under artificial circulation (CPB) and/or valve correction and reconstruction of the LV. The comparison groups did not differ significantly from each other in terms of the volume of surgical intervention performed and the main intraoperative characteristics (Table 6).
Despite the fact that the studied patients in the MG did not differ statistically significantly from the patients in the CG in terms of initial clinical, laboratory and instrumental parameters, the volume of cardiac surgery performed, as well as intraoperative characteristics (Tables 1 and 6), the indicators of tissue metabolism and oxygen balance in the early postoperative period had a number of features (Table 7).
The early postoperative period in the comparison groups was characterized by a statistically significant decrease in the manifestations of metabolic acidosis and tissue hypoxemia, as well as preservation of the efficiency of the oxygen transport function of blood in the MG compared to the CG, which was confirmed in the dynamics of the main parameters of the blood gas composition (Table 7). The data obtained indicate that the positive effect of INH on the functional reserves of the blood gas transport system achieved in the preoperative period was maintained in the early postoperative period, which contributed to a more favorable clinical course of the perioperative period in the MG compared to the CG (Table 8).
Comparative characteristics of the structure of cardiac perioperative complications
A more favorable course of the early postoperative period in patients from the MG compared to the control group was expressed in a decrease in the incidence of perioperative myocardial infarction and “low” cardiac output syndrome, which required long-term cardiotonic support and installation of an IABP system (Table 8).
In the group of patients with ICMP and the use of adaptive hypoxia therapy in preoperative preparation, progression of heart failure in the early postoperative period was significantly less common, which amounted to 3 (8.57%) cases in the MG and 12 (34.29%) in the CG (χ² = 6.87, p = 0.009). One of the main reasons for the severity of the clinical course of the underlying disease in patients in the CG was the more frequent development of PIM (Table 8), which influenced the progression of HF, which was confirmed by a significant increase in the severity marker XCH BNP (374.50 (183.88; 608.01) in the MG and 644.01 (271.01; 955.01) pg/ml in the CG, p=0.022) and a decrease in exercise tolerance according to the results of 6 MTX (350.27±12.31 in the MG and 296.16±18.47 meters in the CG, p=0.017).
Improved perfusion of the hibernating myocardium and the reversibility of ischemic damage to viable cardiomyocytes as a result of revascularization and under the influence of the course of INH, made it possible to ensure the electrical stability of the myocardium and significantly reduce the incidence of life-threatening reperfusion tachyarrhythmias during the restoration of cardiac activity after CPB (7 (20.01%) in the MG and 16 (45.71%) in the CG, χ²=5.25, p=0.022) and prognostically unfavorable cardiac arrhythmias in the early postoperative period – the average daily number of PVCs was 60.00 (22.00; 344.00) in the MG and 565.00 (87.00; 1568.00) in the CG (p=0.004), the average number of PVCs per hour – 2.50 (0.92; 14.33) in the MG and 19.79 (2.86; 65.33) in the CG (p=0.019), PVCs more than 30 per hour – 4 (11.43%) in the MG and 15 (45.45%) in the CG, χ²=8.74, p=0.003).
A more favorable course of the perioperative period in the MG was reflected in a significant reduction in the length of stay of patients in the intensive care unit (Table 8), as well as in the length of hospital stay in the early postoperative period – 15.00 (13.00; 21.00) in the MG and 19.00 (14.00; 24.00) in the CG (p=0.000).
CONCLUSION
Main scientific results
1. A modified method of conducting a ten-day course of intermittent normobaric hypoxic therapy, characterized by a gentle regime of hypoxic training (stepwise increase in the duration of continuous hypoxic exposure and changing the time intervals of hypoxic stimulation and atmospheric air breathing), is characterized by good tolerability, safety and effectiveness of use in preoperative preparation for cardiac surgical treatment of patients with ICMP, including those with FC III-IV severity of CHF [6; 7; 8; 26].
2. Under the influence of intermittent normobaric hypoxic therapy in patients with ICMP, the oxygen capacity of the blood increases due to stimulation of hemoglobin synthesis (from 144.66±3.21 to 153.80±3.09 g/l, p=0.001), the saturation and utilization of oxygen by tissues improves due to an increase in the partial pressure of blood O₂ (from 25.40 (19.80; 31.90) to 28.80 (21.40; 40.10) mm Hg, p=0.015) and the degree of hemoglobin saturation O₂ (from 37.20 (29.70; 59.00) to 44.00 (31.50; 70.10)%, p=0.039), and the severity of metabolic acidosis decreases in the perioperative period: on the 1st day after surgery, the HCO₃⁻ value was 21.90 (20.90; 23.00) in the MG and 20.90 (19.50; 22.50) mmol/l in the CG (p=0.037), the blood lactate level was 1.10 (0.90; 1.40) in the MG and 2.20 (1.50; 4.00) in the CG (p=0.000), the concentration of the actual blood buffer base was -2.20 (-3.40; -0.90) in the MG and -3.60 (-4.90; -2.00) mmol/l in the CG (p=0.009), and the standard blood buffer base – -2.50 (-3.50; -0.90) in the MG and – 3.60 (-5.20; – 1.90) mmol/l in the CG (p=0.014) [6; 8].
3. The course effect of adaptive hypoxic therapy in patients with ICMP promotes activation of the cardiorespiratory system and an increase in the body’s reserve adaptive capabilities, which is expressed in an increase in the level of maximum oxygen consumption (from 11.89±0.59 to 13.69±0.64 ml/kg/min, p=0.009), the value of the double product (from 186.50 (136.50; 214.00) to 197.00 (161.00; 222.00) conventional units, p=0.052), volume of work performed (from 1350.00 (825.00; 2175.00) to 2058.00 (1760.00; 2700.00) kgm, p=0.024), power threshold load (from 50.00 (50.00; 100.0) to 75.00 (75.00; 100.0) W, p=0.023) [8; 24].
4. Clinical use of intermittent normobaric hypoxic therapy in preoperative preparation for cardiac surgical treatment of patients with ICMP contributes to a significant improvement in the perfusion of hibernating myocardium and the reversibility of ischemic damage to viable cardiomyocytes in the area of post-infarction cardiosclerosis: the area of viable myocardium significantly increases (from 84.62 (76.47; 99.82)% to 94.12 (92.31; 100.00)%, p=0.000), the total number of segments with impaired perfusion is reduced (from 7.57±0.53 to 5.89±0.43, p=0.002), as well as the number of segments (from 2.09±0.33 to 0.86±0.20, p=0.000) and area myocardium with severe perfusion defects (from 11.77 (0.00; 23.08)% to 5.88 (0.00; 7.69)%, p=0.001) [6; 8; 13; 20; 21; 22].
5. Improved perfusion of viable myocardium against the background of the training effect of INH helps to increase the electrical stability of the myocardium, which is confirmed by a significant decrease in the amount of prognostically unfavorable ventricular ectopic activity: the incidence of PVCs more than 30 per hour is reduced – from 28.57% to 17.14%, χ² = 8.31, p = 0.004), bigeminy / trigeminy – from 25.71% to 17.14%, χ²=9.50, p=0.002), episodes of nonsustained VT – from 22.86% to 14.29%, χ²=11.61, p=0.001) immediately after INH, and the frequency of life-threatening reperfusion tachyarrhythmias in the process of restoring cardiac activity decreases after CPB (20.01% in the MG and 45.71% in the CG, χ²=5.25, p=0.022) and in the early postoperative period (the average daily number of PVCs was 60.00 (22.00; 344.00) in the MG and 565.00 (87.00; 1568.00) in the CG (p=0.004), the average number of PVCs per hour is 2.50 (0.92; 14.33) in the MG and 19.79 (2.86; 65.33) in the CG (p=0.019), PVCs more than 30 per hour – 11.43% in the MG and 45.45% in the CG, χ²=8.74, p=0.003) [6; 8; 11; 13; 18; 19].
6. The inclusion of the method of intermittent normobaric hypoxic therapy in the preoperative preparation for cardiac surgical treatment of patients with ICMP contributes to a more favorable clinical course of the intraoperative, early and late postoperative periods: the frequency of progression of heart failure is significantly reduced (3 (8.57%) in the MG and 12 (34.29%) in the CG, χ² = 6.87, p = 0.009) due to a decrease in the number of perioperative myocardial infarction (2 (5.71%) in the MG and 7 (20.01%) in the CG, χ²=3.19, p=0.074), low cardiac output syndrome requiring the connection of an IABP (2 (5.71%) in the MG and 8 (22.85%) in the CG, χ²=4.20, p=0.040) and the use of long-term (more than 24 hours) inotropic support (3 (8.57%) in the MG and 12 (34.29%) in the CG, χ² = 6.87, p = 0.009), which allows reducing the total time of stay in the ICU (19.00 (17.00; 41.00) hours in the MG and 24.00 (20.00; 63.00) hours in the CG, p=0.001) and duration of hospital stay in the postoperative period (15.00 (13.00; 21.00) days in the MG and 19.00 (14.00; 24.00) days in the CG, p=0.000), as well as reduce the primary disability due to the progression of CHF during first year after cardiac surgery (3 (8.57%) patients in the MG and 9 (27.27%) patients in the CG, χ²=4.09, p=0.043) [6; 8; 11; 12; 13; 16; 17; 20; 21; 22; 25].
7. The proposed method of preoperative preparation with the additional use of intermittent normobaric hypoxic therapy is economically more effective than traditional preoperative preparation by reducing financial costs by 361.21 US dollars for inpatient treatment of one cardiac surgical patient with ICMP.
Recommendations for practical use of the results
1. All patients with ICMP, if there are indications for cardiac surgical treatment, are recommended to undergo a course of INH in the preoperative period using a modified technique of stepwise adaptation to hypoxic effects.
2. The course of adaptive hypoxic therapy for people with ICMP consists of 10 daily 50-minute sessions of gentle hypoxic training. Each session includes five consecutive 10-minute cycles, in each of which 5-minute intervals of exposure to a hypoxic gas mixture (HGM) alternate with 5-minute intervals of breathing atmospheric air. In the first session of INH, the HGM contains 11% oxygen instead of 10%, and the exposure to continuous hypoxic stimulation in one cycle is 3 minutes and is delivered by alternating 1-minute intervals of exposure to the HGM and 1-minute intervals of breathing with atmospheric air, followed by a stepwise increase from session to session of the duration of continuous hypoxic exposure and changing the time intervals of hypoxic stimulation and breathing with atmospheric air.
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Хирургическая реваскуляризация миокарда – перспективный метод лечения хронической сердечной недостаточности у больных ишемической кардиомиопатией / Ю.П. Островский, А.Г. Булгак, Л.В. Рачок, Т.А. Дубовик, И.В. Сидоренко, А.Ю. Островский, М.Г. Колядко, С.И. Латышев, В.С. Худницкая, В.С. Тихомиров // Кардиология в Беларуси : междунар. науч.-практ. журн. – 2010. – Nº 6 (13). – С. 13-27.
Влияние хирургической реваскуляризации миокарда на жизнеугрожающие нарушения ритма у больных с ишемической кардиомиопатией / Л.В. Рачок, А.Г. Булгак, С.И. Латышев, Т.А. Дубовик, И.В. Сидоренко, М.И. Бельская, В.С. Худницкая // Сердце: журн. для практикующ. врачей. 2010;9(6(56)):335–340.
Использование прерывистой нормобарической гипокситерапии в предоперационной подготовке к коронарному шунтированию у больных ишемической кардиомиопатией / Л.В. Рачок, Т.А. Дубовик, А.Г. Булгак, Ю.П. Островский, М.Г. Колядко, М.И. Бельская, Е.Н. Жуйко, И.И. Русских // Кардиология в Беларуси : междунар. науч.-практ. журн. – 2011. – Nº 4. – С. 28-45.
Влияние прерывистой нормобарической гипокситерапии на компенсаторно-адаптационные возможности организма в комплексной предоперационной подготовке к кардиохирургическому лечению пациентов с ишемической кардиомиопатией / Л.Г. Гелис, Т.А. Дубовик, Л.В. Рачок, Ю.П. Островский, М.Г. Колядко, Т.Т. Геворкян // Кардиология в Беларуси. 2013;5(30):19–38.
Хирургическая реваскуляризация миокарда, как метод лечения сердечной недостаточности у больных ишемической кардиомиопатией / Т.А. Дубовик // Труды молодых ученых 2010: сб. науч. работ / под общ. ред. проф. С.Л. Кабака. – Минск: БГМУ, 2010. – Т. 78. – С. 28-32.
Влияние прерывистой нормобарической гипокситерапии на функциональное состояние сосудистого эндотелия у больных ишемической кардиомиопатией / Т.А. Дубовик, Л.В. Рачок // Дисфункция эндотелия: экспериментальные и клинические исследования: матер. VII Междунар. науч-практ. конф., Витебск, Беларусь, 24-25 мая 2012 г. / Витеб. гос. ун-т ; редкол.: А.П. Солодков (гл. ред.) [и др.]. – Витебск : УО «ВГУ им. П.М. Машерова», 2012. – С. 67-70.
Dobutamine-induced myocardial perfusion improvement in ischemic patients with late post infarction remodeling and severe heart failure / N. Maroz-Vadalazhskaya, L. Rachok, T. Dubovik / Heart Failure Congress 2010 : Abstracts CD, Berlin, May 29 – June 1, 2010 // Eur. J. Heart Failure. – 2010. – Vol. 9 (Suppl. 1). – Abst. P 1112.
Влияние хирургической реваскуляризации миокарда на жизнеугрожающие нарушения ритма у больных с ишемической кардиомиопатией / Л.В. Рачок, А.Г. Булгак, С.И. Латышев, Т.А. Дубовик, И.В. Сидоренко, М.И. Бельская, В.С. Худницкая // Сердечная недостаточность 2010: сб. тез. V Всерос. конгр. Общ-ва специалистов по сердечн. недостаточности, Москва, Россия, 7–8 дек. 2010 г. М., 2010. С.44–45.
Normobaric intermittent hypoxia training as a method of preoperative preparation for coronary bypass surgery of the patients with ischemic cardiomyopathy and chronic heart failure / L.V. Rachok, T.A. Dubovik, I.V. Sidorenko, E.N. Zhujko // 14' Congress of the International Society for Holter and Noninvasive Electrocardiology : abstr. book, Moscow, Russia, April 26-28, 2011 [publ.]. – M.: Medpractika-M, 2011. – P. 56, Abst. P-1-080.
Влияние прерывистой нормобарической гипокситерапии на функциональное состояние сосудистого эндотелия у больных ишемической кардиомиопатией, осложненной хронической сердечной недостаточностью / Т.А. Дубовик / Российский национальный конгресс кардиологов: матер. конгресса, Москва, Россия, 11-13 окт. 2011 г. // Кардиоваскулярная терапия и профилактика. – 2011. – Т. 10. – Nº 6, Приложение 1. – С. 101-102.
Прерывистая нормобарическая гипокситерапия как метод предоперационной подготовки к коронарному шунтированию больных с ишемической кардиомиопатией / Т.А. Дубовик, Л.В. Рачок, Ю.П. Островский / Тезисы ІІ Евразийского конгресса кардиологов // Кардиология в Беларуси: междунар. науч.-практ. журн. – 2011. – Nº 5 (18). – С. 158.
Normobaric intermittent hypoxia training as a method of preoperative preparation for coronary bypass surgery of the patients with ischemic cardiomyopathy and chronic heart failure / L.V. Rachok, T.A. Dubovik, I.V. Sidorenko, E.N. Zhujko / Heart Failure Congress 2011 : Abstracts CD, Gothenburg, Sweden, May 21-24, 2011 // Eur. J. Heart Fail. Suppl. – 2011. – Vol. 10 (Suppl. 1). – P. S108, Abst. P 1112.
Normobaric intermittent hypoxia training as a method of preoperative preparation for coronary bypass surgery of the patients with ischemic cardiomyopathy and its influence on the endothelium functional state / T.A. Dubovik, V.S. Khudnitskaya, L. V. Rachok // II Международный конгресс «Кардиология на перекрестке наук»: тез. докл., Тюмень, Россия, 18-20 мая 2011 г. – Тюмень, 2011. – С. 131-132.
Использование нормобарической гипокситерапии при подготовке к операции коронарного шунтирования / Т.А. Дубовик, Л.В. Рачок, А.П. Шкет // Сердечно-сосудистые заболевания: матер. XVII Всерос. съезда сердечно-сосуд. хирургов, Москва, Россия, 27-30 нояб. 2011 г. / Бюл. НЦССХ им. А.Н. Бакулева РАМН; редкол.: Л.А. Бокерия [и др.]. – М., 2011. – Т. 12. – Nº 6. – С. 61.
Эффективность прерывистой нормобарической гипокситерапии как метода предоперационной подготовки к коронарному шунтированию больных ишемической кардиомиопатией, осложненной хронической сердечной недостаточностью / Т.А. Дубовик, Л.В. Рачок, Ю.П. Островский // Сердечная недостаточность 2011 : сб. тез. VI Всерос. конгр. Общ-ва специалистов по сердечн. недостаточности, Москва, Россия, 8-9 дек. 2011 г. – М., 2011. – С. 20.
Normobaric intermittent hypoxia training as a method of sudden cardiac death primary prevention in the patients with ischemic cardiomyopathy / T.A. Dubovik, L.V. Rachok, A.P. Shket, V.S. Khudnitskaya / 14" WorldCongress of the Society of Arrhythmias : Abstracts book, Athens, Greece, December 11-14, 2011 // Pacing and Clinical Electrophysiology. – 2011. – Vol. 34, N° 11. – P. 1362-1451, Abst. P 160.
Hypoxic adaptation and arrhythmia prevention in patients with ischemic cardiomyopathy and chronic heart failure / T.A. Dubovik, L.V. Rachok / Heart Failure Congress 2012 : Abstracts CD, Belgrade, Serbia, May 19-22, 2012 // Eur. J. Heart Fail. Suppl. – 2012. – Vol. 11 (Suppl. 1). – P. S189, Abst. P 1023.
Hypoxic adaptation as a method of preoperative preparation for cardiovascular surgery in the ischemic cardiomyopathy patients / T. Dubovik, L. Rachok, Y. Ostrovsky // 4" Joint Scandinavian Conference in Cardiothoracic Surgery: Abstracts book, Vilnius, Lithuania, August 16-18, 2012. – Vilnius, 2012. – P. 68.
Прерывистая нормобарическая гипокситерапия как эффективный метод предоперационной подготовки к кардиохирургическому лечению больных ишемической кардиомиопатией / Т.А. Дубовик, Л.В. Рачок // III Международный конгресс «Кардиология на перекрестке наук»: тез. докл., Тюмень, Россия, 16-18 мая 2012 г. – Тюмень, 2012. – С. 89-90.
Normobaric intermittent hypoxia adaptation as a method of preoperative preparation for cardiovascular surgery / L.G. Gelis, T.A. Dubovik, L.V. Rachok, Y.P.Ostrovsky // 31st International Cardiovascular Surgery Symposium : final programme, Zürs, Austria, March 2-9, 2013. – Zürs, 2013. – P. 3.
Effects of hypoxic adaptation on the endothelial dysfunction in the ischemic cardiomyopathy patients / M.G. Kaliadka, L.G. Gelis, L.V. Rachok, T.A. Dubovik, I.I. Russkih // Biochimica clinica. – 2013. – Vol. 37, (Special Suppl.). – P. S538
Effects of hypoxic adaptation on the exercise intolerance and the adaptation reserves level in patients with ischemic cardiomyopathy / T. Dubovik, L. Gelis, L. Rachok / Heart Failure Congress 2013 : Abstracts CD, Lisbon, Portugal, May 25-28, 2013 // Eur. J. Heart Fail. Suppl. – 2013. – Vol. 12. – P. S148, Abst. P 1468.
Preoperative hypoxic adaptation in the prevention of perioperative complications after cardiovascular surgery / L.G. Gelis, T.A. Dubovik, Y.P. Ostrovsky, L.V. Rachok // 28' Meeting of the Association of Cardiac Surgeons: final programme, Madrid, Spain, June 20-22, 2013. – Madrid, 2013. – P. 23.
Инструкция по применению Nº 202-1210 от 08.04. 2011 г. «Методика применения интервальных гипоксических тренировок у пациентов с ишемической кардиомиопатией при подготовке к операции коронарного шунтирования в условиях искусственного кровообращения» / А.Г. Булгак, Ю.П. Островский, Л.В. Рачок, М.Г. Колядко, И.В. Сидоренко, М.И. Бельская, Е.Н. Жуйко, Т.А. Дубовик, В.И. Терехов, Н.В. Феоктистова, Е.Н. Лашкевич. – Минск, 2011. – 7 с.
Full main-text translation: T.A. Dubovik. Intermittent normobaric hypoxic therapy in preoperative preparation for cardiac surgical treatment of patients with ischemic cardiomyopathy. Candidate thesis abstract. Minsk, 2013. 24 pp.
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