Abstract
The purpose of this study was to study the effectiveness of using intermittent normobaric hypoxic therapy (INH) as a method of preoperative preparation for coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB) in patients with ischemic cardiomyopathy (ICMP) complicated by chronic heart failure (CHF). The study included 60 male patients with an established diagnosis of ICMP (n=30 in the main and control groups). All patients had a left ventricular ejection fraction (LVEF) less than 35% and NYHA stage II–IV CHF. Patients of the main group at the stage of preparation for CABG underwent a course of INH using the Bio-Nova-204G1 installation.
The indication for CABG surgery was the presence of at least 50% of the myocardium with radiopharmaceutical accumulation of more than 50% in the presence of a well-developed distal bed and the absence of severe right ventricular failure. All patients underwent coronary angiography, echocardiography, day-long electrocardiogram monitoring, myocardial scintigraphy, and ultrasound examination of the brachial artery against the background of a reactive hyperemia test. Markers of endothelial dysfunction and the severity of CHF were studied: endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), homocysteine. The initial severity of CHF in the study and control groups was determined by a violation of the contractile function of the LV (LVEF was 29.33±1.23% and 29.06±1.32%, respectively) against the background of dilatation of the LV cavity and the predominance of the activity of the sympathetic nervous system.
Patients in both groups showed changes in the functional state of the endothelium. In 73% in the main group and 64% in the control group, impaired vasodilation and vasoconstrictor reactions predominated. After using the course of INH in the preoperative period before CABG, in the main group there was a shift in the autonomic balance towards the predominance of the tone of the parasympathetic nervous system (an increase in the RMSSD indicator from 38.6 ± 4.5 ms to 58.22 ± 6.1, p<0.05), a decrease in the total number of ventricular arrhythmias (ventricular arrhythmias) against the background of improved microcirculation processes.
The myocardial area with moderate and severe hypoperfusion decreased from 35.6 to 30.2% and from 16.5 to 14.2%, respectively. The parameters of the systemic blood flow significantly changed: the diameter of the brachial artery after the test with reactive hyperemia increased from 4.51±0.12 to 4.88±0.12, an increase in the Gosling pulsation index was recorded by 26.36% (from 3.87±0.31 to 4.89±0.41, p<0.05), ET-1 levels significantly decreased with 2.74±0.18 to 1.98±0.16, TNF-α – from 24.31±3.7 to 13.21±3.2 and homocysteine – from 15.69±1.2 to 12.33±0.9). The main group was characterized by a more favorable course of the perioperative period: ventricular fibrillation was significantly less common during the recovery of cardiac activity after cardiopulmonary bypass, and long-term inotropic support was used significantly less frequently.
In the main group, perioperative myocardial infarction was diagnosed significantly less often, and the frequency of occurrence of ventricular arrhythmias and high-grade ventricular arrhythmias in the early postoperative period was significantly less frequent. In the patients of the main group in the postoperative period, positive dynamics in changes in the functional state of the endothelium remained in comparison with the control group. The use of INH in patients with ICMP complicated by CHF in preparation for CABG surgery, provided there is a sufficient mass of viable myocardium in the territory of the revascularized arteries, can improve the functional state of the endothelium and microcirculatory processes, helps reduce prognostically unfavorable ventricular ectopic activity.
All this ensures a more favorable course of the perioperative period and prognosis in this category of patients.
Introduction
Coronary heart disease (CHD) is one of the most widespread diseases of our time, which in most countries has a tendency to grow, rejuvenate and spread to various categories of the population [1, 2]. A special position in the general structure of coronary heart disease is occupied by patients with signs of chronic heart failure (CHF), which is a natural outcome of the development of coronary artery disease [3-6]. According to the results of special epidemiological and multicenter studies in recent years, ischemic etiology of heart failure (HF) was noted on average in 64% of patients, and survival in this category of patients was significantly lower than in patients with HF of other etiology, which is due to a more unfavorable course of the underlying pathological process [2, 5, 7-13].
Advances in recent years in the field of studying the pathogenesis and mechanisms of progression of heart failure against the background of coronary artery disease have led to the formation of the concept of the “cardiovascular continuum”, one of the key links of which is the structural remodeling of the heart after myocardial infarction, which triggers a “vicious circle” of pathological processes in the myocardium, including stretching, hypertrophy, “architectural” restructuring and apoptosis of cardiomyocytes. All this contributes to dilatation of the heart chambers and the occurrence of left ventricular (LV) systolic dysfunction [14-16]. Another significant factor in the development of CHF against the background of coronary artery disease is the constant participation in this process of persistent and/or permanent coronary insufficiency, which leads to the formation of “stunned” or “hibernating” myocardium, with the gradual development of hypocontractility the entire myocardium and progression of LV dysfunction.
Decompensation of HF in patients with coronary artery disease is caused not only by ventricular dysfunction, but also by the constant participation in this process of excessive activation of neurohormonal systems and vascular remodeling, manifested by a progressive increase in vascular resistance, decreased elasticity of the vascular walls and dysfunction of the endothelium of the coronary vessels [17].
The presence of occlusive lesions of the coronary arteries in the pathogenesis of HF developing against the background of coronary artery disease does not allow success in its prevention and treatment without adequate revascularization of the heart muscle [18]. However, the choice of treatment tactics for patients with ischemic myocardial dysfunction in combination with CHF has remained a constant subject of debate in recent years. The question remains unclear whether surgical revascularization of the myocardium can influence the prognosis in this category of patients at advanced stages of CHF [19-20]. Conflicting views on the existing problem are due to a significant number of postoperative complications leading to an increase in the duration of treatment, a decrease in the effectiveness of rehabilitation measures and a deterioration in the long-term results of surgical treatment.
Despite the achievements and accumulated experience of surgical treatment of patients with ischemic cardiomyopathy (ICMP), postoperative mortality after coronary artery bypass grafting (CABG) in this category of patients remains high and, according to some authors, reaches 16.9% [19, 21]. It remains generally accepted that perioperative mortality in patients with CHF inversely correlates with the value of LV ejection fraction [20].
Thus, it becomes relevant to search for new methods of preoperative preparation of this category of patients in order to reduce the number of perioperative complications and improve long-term results of surgical myocardial revascularization. Recognition of the fact that CHF against the background of coronary artery disease has a polygenic pathogenesis, caused not only by a decrease in the contractility of the heart muscle, but also by a complex of interrelated hemodynamic, metabolic and neurohumoral disorders leading to a decrease in the effectiveness of adaptation mechanisms, currently there has been increased interest in the use of non-drug methods for increasing the body’s nonspecific resistance to a stress factor, which is surgery.
In recent years, the use of adaptation to the hypoxic factor in normobaric conditions using Intermittent normobaric hypoxic therapy (INH) is one of the most promising methods for increasing the adaptive capabilities of the body [23-31]. This is based on the metabolic adaptation of the myocardium to transient ischemia, called the phenomenon of “ischemic preconditioning” [32]. The essence of this phenomenon is to increase resistance to the damaging effects of prolonged disruption of coronary blood flow some time after episodes of intermittent short-term myocardial ischemia, which provides a cardioprotective effect and determines the protection of the myocardium from ischemic and reperfusion damage and toxic concentrations of catecholamines [33].
Purpose of the study
The purpose of this study was to study the effectiveness of using intermittent normobaric hypoxic therapy as a method of preoperative preparation for CABG surgery under cardiopulmonary bypass (CPB) in patients with ICMP complicated by chronic heart failure.
Material and methods
The present study included 60 male patients with an established diagnosis of ICMP using a purposive sampling method. The diagnosis of ICMP was established on the basis of standardized diagnostic criteria: the presence of indications of a previous myocardial infarction (MI), echocardiography parameters (LV end-diastolic size greater than 55 mm, LV ejection fraction (EF) less than 35%, local contractility index greater than 1.3, relative LV wall thickness index less than 0.45), diagnosed stenotic lesions of the coronary arteries and the presence of symptoms of heart failure [3, 22, 34, 35].
Patients with non-ischemic cardiomyopathy were excluded from the study; hemodynamically significant disturbances of blood flow in the extracranial region; organic pathology of the valve apparatus requiring surgical correction; pathology of the thyroid gland requiring drug correction; insulin-dependent diabetes mellitus; primary or secondary erythrocytosis; individual intolerance to lack of oxygen.
Using the matched-pair method [36], we formed two groups – the main group, which received a course of INH in the preoperative period, and the control group. The groups were representative according to basic clinical and anamnestic data (Table 1). To objectify the functional class (FC) of HF, the New York Heart Association NYHA classification was used, supplemented by data from the 6-minute walk test [37]. All patients had their surgical risk calculated before surgery according to the European risk classification for heart surgery – EuroScore [38].
Instrumental and clinical laboratory examinations of patients were carried out twice (before surgery and on the 14th day after CABG) in the control group and three times (initially, after a course of INH and on the 14th day after CABG) in the main group.
Instrumental examination included day-long electrocardiogram monitoring (CM-ECG), coronary angiography, transthoracic echocardiography (EchoCG), single-photon emission computed tomography with 99mTc-MIBI (SPECT with 99mTc-MIBI) and assessment of endothelial function with ultrasound examination of the brachial artery against the background of a reactive hyperemia test.
SM-ECG was carried out using Philips zymed holter Holter monitors with an assessment of the frequency of arrhythmias (in% of the total number of patients), the total number of rhythm disturbances during monitor observation, the severity of arrhythmias, the number and duration of episodes of ST segment depression. Temporal analysis of heart rate variability (HRV) was performed. The following parameters were assessed: SDNN, ms—standard deviation of normal RR intervals; SDANN, ms—standard deviation of RR interval values averaged over 5 minutes; RMSSD, ms — square root of the average value of the squared differences in the durations of successive RR intervals.
Selective coronary angiography was performed using an Innova 3100 digital angiographic device (GE, USA) according to standard generally accepted methods [39].
Cardiohemodynamic abnormalities were assessed by echocardiography performed according to a standard protocol using the recommendations of the American Society of Echocardiography [40, 41].
To assess the state of myocardial perfusion, all patients underwent SPECT with 99mTc-MIBI on a single-photon emission computed tomograph “Nucline X-Ring/R” [42]. The severity of disturbances in LV myocardial perfusion was visualized in the form of a decrease in the accumulation of radiopharmaceuticals (RP) in relation to the intact myocardium. The following degrees of myocardial perfusion impairment were distinguished: normal perfusion (the level of accumulation of radiopharmaceuticals above 75% of the maximum accumulation), “moderate decrease in perfusion” (from 51 to 75%), “marked decrease in perfusion” (from 31 to 50%), and aperfusion or “sharp decrease in perfusion” (less than 30%), which was considered as scar changes [43].
The indication for CABG surgery was the presence of at least 50% of the myocardium with radiopharmaceutical accumulation of more than 50% [44, 45].
Ultrasound examination of the brachial artery (BA) with a test with reactive hyperemia was performed according to the standard technique [46]. The following parameters were assessed: D – initial BA diameter, Ds – BA diameter after a test with reactive hyperemia, RI (Purcelot index) – peripheral vascular resistance index, PI (Gosling index) – pulsation index characterizing the elastic properties of the vascular wall. Endothelium-dependent vasodilation (EDVD, %) was calculated as the ratio of the change in BA diameter during reactive hyperemia to the artery diameter at rest [46].
Laboratory examination of patients included determination of the level of endothelin-1 (ET-1), as well as pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the serum of patients using DRG diagnostic kits (International Inc, USA) by enzyme-linked immunosorbent assay with detection on a microplate enzyme-linked immunosorbent analyzer Sunrise Reader (Tecan, Austria) and Access 2 (Beckman Culter, USA), respectively. To objectify the severity of HF, assess prognosis and monitor the effectiveness of therapy, the level of brain natriuretic peptide (BNP, pg/ml) in whole blood [47, 48] containing EDTA was measured in all patients using a Triage-Meter immunofluorescence analyzer (Biosite Diagn., USA).
The level of homocysteine, which is a criterion for the unfavorable clinical course of IHD and an independent risk factor for cardiovascular accidents [29], was studied using the Architect 2000 SR analyzer (Abbott, USA).
To analyze the effectiveness of the course of INH in the venous blood of patients in the main group, parameters of the gas composition were determined, which indirectly reflect tissue oxygenation and the degree of its adequacy in relation to the metabolic demands of the body. We assessed the following indicators: partial pressure (tension) of oxygen (pO₂, mm Hg) and the concentration of total O₂ associated with hemoglobin and physically dissolved in the blood plasma (ctO₂), reflecting the supply, content and transport of oxygen in the blood; blood oxygen tension at 50% blood desaturation (p50) – an indicator characterizing the release of oxygen to tissues; blood oxygen saturation (sO₂) is an indicator that indirectly reflects cardiac output, oxygen delivery to tissues and its utilization; as well as the concentration of lactate (cLac) in the blood, which serves as a marker of imbalance between oxygen consumption by tissues and its needs and characterizes the adequacy of tissue metabolism [49].
These parameters were assessed using a blood gas and electrolyte analyzer Radiometer ABL800FLEX (Denmark).
All patients underwent CABG surgery using arterial and venous grafts under conditions of extracorporeal circulation and using a complex blood-based method of myocardial protection. In 57.4% of cases in the main group and in 58.3% in the control group, mitral valve (MV) plasty on a support ring was performed simultaneously with CABG to correct relative MV insufficiency. The indications for surgical myocardial revascularization were the generally accepted indications for CABG in patients with coronary artery disease [18] in the presence of a well-developed distal bed and the absence of severe right ventricular failure (right ventricular EF less than 35%) [50].
As can be seen from the data presented in Table 2, there were no statistically significant differences between the groups in terms of the characteristics of the surgical intervention and the indicators of the intraoperative period.
The assessment of the intraoperative period was carried out based on the analysis of protocols of the operation and transfusion charts, and the nature of the recovery of cardiac activity after cardiopulmonary bypass was studied. In the postoperative period, the number and nature of perioperative complications were analyzed.
Statistical data processing was carried out using standard software packages Statistica (version 6.1), Microsoft Office Excel 2003, Statplus, Biostat. The results are presented in the form M±m, where M is the arithmetic mean, m is the standard error of the arithmetic mean for a normal distribution. The normal distribution of the studied indicators in the two groups was checked using the Kolmogorov-Smirnov method. The significance of differences between characteristics with a normal distribution was assessed using Student’s t-test for related and unrelated samples. Characterization of qualitative characteristics was carried out by assessing the proportion of individuals with this characteristic in the group using the χ² goodness-of-fit criterion.
The relationships between the studied indicators within the group and between groups were studied using the Pearsona correlation analysis method. The differences were considered reliable at a probability level of 95% (p<0.05).
Intermittent normobaric hypoxic therapy protocol
Patients of the main group, at the stage of preparation for surgical intervention, in order to increase the nonspecific resistance of the body, received a course of intermittent normobaric hypoxic therapy using a gas separation membrane installation for hypoxic therapy “Bio-Nova-204G1” (Russia). INH was carried out based on the methodological recommendations of the USSR Ministry of Health and the Russian Ministry of Health, the results of modern researchers [24, 30, 31, 53] and the development of a modified protocol for stepwise adaptation to periodic hypoxia for patients with CHF. Using the apparatus, a gas mixture containing 10±1% oxygen and 90±1% nitrogen gas was supplied at normal atmospheric pressure.
INH sessions were carried out in a cyclic-fractional mode using mask breathing. The total time of hypoxic exposure for 1 session ranged from 15 to 25 minutes with a total session duration of 55 minutes. The course of treatment consisted of 10 daily sessions using a stepwise scheme of adaptation to periodic hypoxia. To determine individual sensitivity to hypoxia and study the hemodynamic response, all patients underwent an acute hypoxic test before starting a course of INH (for 10 minutes the subject breathed a “standard” hypoxic gas mixture containing 10% oxygen). Throughout the course of INH, minute-by-minute registration of arterial blood oxygen saturation (SpO₂), monitoring of hemodynamic parameters (blood pressure, heart rate), ventilation parameters (respiratory rate) was carried out, and electrocardiogram data recorded using a Hewlett Packard M3046A bedside monitor was assessed.
Before starting the INH course and Immediately after its completion, to assess the individual compensatory and adaptive capabilities of the body, the Stange test (maximum breath holding time during inhalation) was performed, which characterizes the body’s resistance to mixed hypercapnia and hypoxia [53].
Results
Assessment of the initial condition of patients with ICMP
Initially, all studied patients of both groups had a severe clinical condition due to a high functional class of HF (Table 1). The BNP level, as a marker of the severity of CHF, was 558.9±108.1 pg/ml in the main group and 567.8±109.2 in the control group. The severity of CHF, as well as the severity of dysfunction of the neurohumoral and endothelin systems in the studied patients, was indirectly indicated by the high level of ET-1, pro-inflammatory cytokines (IL-6 and TNF-α), homocysteine (Table 7), which was associated with an unfavorable prognosis in this category of patients [54-57].
The changes described above in patients of both groups were recorded against the background of pronounced morphofunctional changes in the LV. In both groups, there was a significant increase in LV volumes (LV EDV and LV ESI were 271.8 ± 19.8 ml and 96.9 ± 0.21 ml/m² in the main group and, respectively, 269.14 ± 14.9 ml and 94.98 ± 0.13 ml/m² – in the control group) against the background of a decrease in its contractility while maintaining the size and function of the RV (RV EDV and EF were, respectively) 55.25±6.24 and 51.6±3.65 – in the main group and 54.7±8.5 and 52.1±7.3% – in the control group).
Both groups were characterized by a violation of the LV geometry – the process of LV dilatation prevailed over the process of myocardial hypertrophy, which was reflected in the nature of changes in the sphericity index and IOT of the LV wall (Table 1). The index of local contractility of the LV myocardium was 2.23±0.07 in the main group and 2.31±0.26 in control.
According to the results of SPECT with 99mTc-MIBI, the number of LV myocardial segments with hypoperfusion averaged 4.7±1.9 in the main group and 5.5±1.9 in the control group. In 35.6% of LV segments of the main group and in 37.6% of the control group, a moderate decrease in perfusion was observed, in 16.5 and 14.5%, respectively, a pronounced decrease in perfusion, and in 4.4 and 5.3%, respectively, a sharp decrease in perfusion (Fig. 1).
The severity of CHF manifestations in patients of both groups was characterized by the frequent occurrence of prognostically unfavorable ventricular ectopic activity, which indirectly reflected electrical instability of the myocardium and a high risk of sudden cardiac death in patients with ICMP [58,59].
Ventricular ectopic activity in both groups was recorded against the background of sinus tachycardia. The average heart rate in the main group was 93.23±2.49 beats per minute and 92.7±1.89 beats in the control group. Sinus tachycardia in the group of patients with ICMP was essentially a response of the automatic cells of the sinus node to myocardial ischemia and decreased contractile function of the heart, as well as the predominance of the tone of the sympathetic nervous system (SNS), which was reflected in the initially low values of SDNN, SDANN and RMSSD indices in both groups (Table 3).
Analysis of day-long monitoring of ECG parameters did not reveal statistically significant differences between the groups at the preoperative stage: patients in both groups had ventricular arrhythmias (ventricular arrhythmias) in 100% of cases. Average number of ventricular extrasystoles per hour in the control group was 51.3±0.87, in the main group – 45.7±1.9, almost half of the patients had ventricular arrhythmias of high grades (Table 3). All ventricular arrhythmias were in most cases asymptomatic and were not accompanied by hemodynamic disturbances. The largest number of ventricular arrhythmias were recorded against the background of myocardial ischemia: the average number of episodes of ST segment depression per day in the study and control groups was 4.48±0.24 and 5.12±0.18 minutes.
The occurrence of persistent and paroxysmal forms of atrial fibrillation (AF) in 29.9% of patients in the main group and in 33.3% of the control group is probably due to LA stretching against the background of dilatation of the LV cavity.
When conducting a Pearson correlation analysis, an inverse average strength and strong statistically significant correlation was established between HRV indicators and the number of PVCs greater than 30/hour (SDNN – r=-0.68, p<0.05; R=-0.89; p<0.05; SDANN – r=-0.75, p<0.05; R=0.72; p<0.05; RMSSD – r=-0.85; R=0.84; p<0.05), which indirectly indicated the significant influence of autonomic imbalance on the incidence of ventricular arrhythmias. When assessing endothelial function based on the analysis of EDVD against the background of a test with reactive hyperemia, it was found that in the main group, 27% of patients maintained normal vasodilating function of the endothelium, and in the control group this level was 36%.
Insufficient vasodilation was observed in 55 and 48% of patients in both groups, respectively. Post-occlusive vasoconstriction of the BA in the main group occurred in 18% of patients, and in the control group – in 16% (Fig. 2). All of the above indicated a significant predominance in the studied groups of patients with impaired EDVD.
Effects of the hypoxic therapy course
The effectiveness of INH was assessed by studying the dynamics of parameters of the cardiorespiratory system and blood gas composition (Table 4).
The change in blood gas composition was manifested in an increase in the partial oxygen tension in the venous blood (pO₂ increased from 27.5 initially to 38.7 mm Hg after a course of INH, p<0.05) and an increase in arterial blood oxygen saturation during INH (SpO₂ increased from 90.3 to 97.5%, p<0.05). These changes indicated the activation of adaptive-compensatory mechanisms against the background of hypoxic exposure. A significant increase after a course of INH in SO₂ indicators by 21.8% (from 55.4±3.1 to 67.5±2.3, p<0.05), CtO₂ by 48.4% (from 9.3±0.36 to 13.8±0.19, p<0.05) and p50 by 16.5% (with 23.7±0.48 to 27.6±0.36, p<0.05) reflected an improvement in oxygen transport in the blood, its delivery, release and utilization by tissues.
This was confirmed by a decrease in lactate levels by 56.9% (from 2.11±1.7 to 0.91±0.6, p<0.05). Significant increase in the time of performing the Stange test under the influence of INH indicated improved regulation of alveolar aeration and capillary pulmonary blood flow under the influence of adaptation to the hypoxic factor [60].
Activation of microcirculatory processes against the background of INH was indirectly confirmed by data obtained from SPECT with 99mTc-MIBI (Fig. 3). After a course of intermittent hypoxic therapy, patients in the main group showed a decrease in the myocardial area with moderate and severe hypoperfusion and an increase in the area with normoperfusion. The number of LV myocardial segments with moderate and severe perfusion defects decreased from 4.7±1.9 to 3.5±0.8 (p<0.05).
Of particular interest were the results of SM-ECG after the course of INH. There was a significant decrease in average heart rate, which was due to a decrease in the activity of the sympathetic nervous system and an increase in the influence of the parasympathetic nervous system on the sinus node and baroreflex mechanisms of heart rate regulation. This was reflected in a significant increase in the RMSSD indicator (from 38.6 ± 4.5 ms to 58.22 ± 6.1 ms, p<0.05). There was a trend towards a decrease in the total number of ventricular arrhythmias, the average number and total duration of ST segment depression episodes per day (Table 3), which was most likely due to an improvement in microcirculatory processes in the LV myocardium and a shift in the autonomic balance towards the influence of the parasympathetic nervous system.
After using the INH course in the main group, we noted positive dynamics in changes in the functional state of the endothelium, which was reflected in an increase in the number of patients with normal EDVD from 27 to 60% (Fig. 4) and in a statistically significant decrease in the levels of homocysteine, endothelin-1 and TNF-α (Table 7).
When assessing the quantitative parameters of systemic blood flow in the brachial artery after a course of INH (Table 5), we noted a significant increase in the diameter of the brachial artery during the test with reactive hyperemia from 4.51±0.12 to 4.88±0.12 at the preoperative stage and from 4.41±0.11 to 4.75±0.12 in the postoperative period. An increase in the Gosling pulsation index was recorded by 26.36% (from 3.87±0.31 to 4.89±0.41, p<0.05).
The emerging changes reflected an improvement in the elastic properties of the vascular wall under the influence of INH and indirectly indicated an improvement in tissue perfusion. When conducting a correlation analysis, mutual positive correlations were revealed between the parameters of blood oxygen saturation and the increase in the diameter of the brachial artery in response to reactive hyperemia (r = 0.658, p<0.05).
Comparison of the intraoperative and early postoperative period after CABG
Analysis of the intra- and postoperative period in both groups revealed that in the group of patients who underwent a course of INH, ventricular fibrillation was less common during the restoration of cardiac activity after CPB. The number of cases of “low” cardiac output syndrome, requiring the connection of intra-aortic balloon counterpulsation (IABP) and the use of long-term inotropic support with sympathomimetics intraoperatively and in the early postoperative period, was also lower in this group than in the control group. We noted a more favorable course of the early postoperative period in the main group – the occurrence of perioperative myocardial infarction and manifestations of postcardiotomy syndrome were diagnosed much less frequently (Table).
The nature of changes in endothelial function and the occurrence of rhythm disturbances in the postoperative period had a number of features in both study groups.
Surgery had a negative impact on changes in the vasodilating function of the endothelium among patients in the control group: the percentage of patients with vasoconstrictor reactions increased more than 3 times (from 16 to 72%, p<0.05). This occurred due to a decrease in the number of patients with normal endothelial function (from 36 to 7%, p<0.05), as well as patients with insufficient vasodilation (from 48 to 21%, p<0.05). On the contrary, in patients of the main group, the positive effect achieved in the preoperative period after a course of INH in terms of the dynamics of changes in EDVD was maintained – normal EDVD was found in 60% of patients, reduced EDVD – 20%, vasoconstriction – 20% (Fig. 4 and 5).
The postoperative period was characterized by significant changes in biochemical markers of endothelial dysfunction, which were significantly expressed in the control group. Thus, the levels of ET-1, IL-6, TNF-α and homocysteine in the control group were statistically significantly higher than those in the main group (Table 7), which suggested a more favorable prognosis in patients who underwent a course of INH in the preoperative period.
The early postoperative period in both study groups was characterized by the frequent occurrence of paroxysmal atrial fibrillation (20.0% in the main group and 33.3% in the control group), which was caused by traumatic remodeling of the atria [14, 61, 62]. The highest incidence of this rhythm disorder in the control group may be associated with a longer period of cardiopulmonary bypass (Table 2) and more frequent use of cardiotonic support in the control group, which is confirmed by the identified direct, moderately strong, statistically significant correlation between the time of cardiopulmonary bypass and the incidence of AF (r = 0.68, p<0.05).
Along with this, there was a significant decrease in the incidence of ventricular arrhythmias and the number of high grade ventricular arrhythmias both in the main group and in the control group. Possible mechanisms for reducing ectopic myocardial activity in patients with ICMP after CABG surgery are an increase in coronary blood flow and LV remodeling processes. When conducting a correlation analysis, a direct, moderately strong, statistically significant relationship was established between the values of the CSI and the incidence of PVCs in the control and main groups (r = 0.48, p<0.05; r = 0.35, p<0.05, respectively).
Discussion
Intermittent normobaric hypoxia therapy had a significant effect on the key links of the cardiovascular continuum – endothelial dysfunction and neurohumoral hyperactivation. The course of INH was accompanied by a significant improvement in the functional state of the endothelium, while the ability of blood vessels to dilate increased. Adaptive hypoxia therapy in the main group of patients led to a decrease in the influence of the sympathetic part of the autonomic nervous system and an increase in the role of parasympathetic effects on the regulation of heart rate. This, in turn, was accompanied by a decrease in average heart rate, a decrease in the incidence of reperfusion arrhythmias intraoperatively and the occurrence of ventricular arrhythmias in the early postoperative period.
Apparently, the limitation of adrenergic effects on the myocardium, as well as metabolic adaptation of the myocardium, formed in patients during the course of INH underlie the reduction in the number of ischemic and reperfusion injuries of the heart in the main group compared to the control group.
A significant effect of adaptation to intermittent normobaric hypoxia was a significant impact on the oxygen transport function of the blood. Against the background of INH, the oxygen capacity of the blood increased and the efficiency of oxygen delivery to the periphery increased as a result of adaptive changes in the microcirculation system.
Thus, we associate the more favorable course of the intra- and postoperative period in patients of the main group who underwent a course of INH in the preoperative period with an increase in myocardial resistance to ischemic and reperfusion damage against the background of improved myocardial perfusion, activation of stress-limiting systems and stabilization of neurovegetative regulation processes, which ensures more adequate adaptive responses of the organs and systems of the patient’s body to the stress effects caused by surgical intervention under conditions of cardiopulmonary bypass.
Conclusions
Adaptation to intermittent normobaric hypoxia in patients with ICMP complicated by CHF is accompanied by an improvement in the functional state of the endothelium and endothelium-dependent mechanisms for regulating vascular tone, which leads to a decrease in peripheral vascular resistance and an improvement in the elastic properties of the vascular wall.
The use of INH in the preoperative period in patients with ICMP leads to an improvement in the oxygen transport function of the blood by increasing oxygen capacity and improving the transport and metabolism of oxygen in tissues, and thereby providing improved myocardial perfusion.
The course of adaptation to intermittent normobaric hypoxia helps to optimize the functional indicators of the cardiorespiratory system and the body’s economical use of oxygen, increases tolerance to hypoxia, which is reflected in the normalization of central hemodynamic parameters during the course of INH.
The use of INH in patients with ICMP leads to a decrease in prognostically unfavorable ventricular ectopic activity by limiting the adrenergic effect on the myocardium.
Intermittent normobaric hypoxia therapy is a significant factor that allows it to have a beneficial effect on the course of the perioperative period, which increases the effectiveness of cardiac surgical treatment.
The list of references is in the editorial office.
References
Full main-text translation: L.V. Rachok, T.A. Dubovik, A.G. Bulgak et al. Use of intermittent normobaric hypoxic therapy in preoperative preparation for coronary artery bypass grafting in patients with ischemic cardiomyopathy. Cardiology in Belarus. 2011;4(17):28–45.
Related resources
Related resources on hypoxic training technology and applications.