Introduction
Arterial hypertension is among the most common chronic diseases, characterised by blood pressure above 140/90 mmHg. The diagnosis is made when elevated pressure is detected over four weeks. Prevalence in older age groups reaches 60% or more [1, 2]. Hypertension is a decisive risk factor for cardiovascular complications, including acute and chronic coronary insufficiency and reduced myocardial contractility; cerebrovascular complications, including acute and chronic circulation disorders; and kidney complications [3, 4]. Among recognised vascular-catastrophe risk factors, hypertension ranked fourth by increase as a principal cause, rising 6.7% from 2005 to 2021 [5, 6]. Raised blood pressure causes asymptomatic organ damage.
The projected number of patients by 2025 was almost 1.6 billion [7]. Adult prevalence of 30–45% highlights the importance of treatment and prevention research [8]. Drug intolerance, multiple adverse effects, difficulty adjusting doses and dosing frequency according to individual needs explain the search for new nonpharmacological treatments.
Normobaric interval hypoxic therapy (IHT) has long been used for respiratory, cardiovascular, endocrine and nervous-system diseases and anaemias [9, 10, 11]. Academician N.N. Sirotinin first attempted to combine hypoxic and oxygen therapy for various disorders in the last century [12]. However, relatively few studies address the pathophysiological mechanisms of enteral oxygen therapy and IHT in hypertension. A comprehensive assessment was therefore needed to substantiate normobaric hypoxic therapy combined with oxygen cocktails for hypertension.
Study objective
The objective was comprehensive investigation of stage I hypertension to substantiate the combined use of interval normobaric hypoxic therapy and enteral oxygen therapy pathophysiologically.
Materials and methods
The study included 170 men aged 45–65, mean age 52.3, with diagnosed stage I hypertension. Fifty-five received standard antihypertensive therapy alone, without hypoxic or oxygen therapy, as the comparison group.
Oxygen consumption was calculated by the Douglas–Haldane method. Lung function was tested using a portable Spiro PRO spirometer, BTL-08 (UK/Czech Republic). Echocardiography used a Philips CX50 (Netherlands). Blood pressure was measured by the classical Korotkov method.
All patients had blood counts with differential and ESR. Lipid testing measured cholesterol, HDL, LDL, VLDL and triglycerides. LPO activity was assessed by blood malondialdehyde using V.B. Gavrilov’s method; erythrocyte glutathione peroxidase by V.M. Mein’s method; and serum superoxide dismutase (SOD) by Nishikimi’s method. Laboratory investigations were performed at the Medical Consultative and Diagnostic Centre of the Kabardino-Balkarian Ministry of Health.
Myocardial bioelectrical properties were studied with a Schiller CARDIOVIT AT-101 (Switzerland), recording 12-lead ECGs. Treatment effectiveness was assessed from 24-hour blood-pressure profiles before and after treatment and Holter ECG monitoring with a BTL-08 HOLTER H600 (UK/Czech Republic).
Hypoxic therapy used the Hypo-Oxy hypoxicator from Oxyterra (Russia), alternating the required hypoxic mixture with ambient air. A pre-treatment hypoxic test determined starting oxygen concentration. Patients breathed 14% oxygen for the first five days, 13% for the next five, and 12% for the final five, progressively lowering inspired oxygen to engage adaptation. Enteral oxygen therapy consisted of oxygen cocktails prepared with a Lonfian JAY-8 concentrator–cocktail maker (China). Statistical analysis assessed quantitative distributions for normality using chi-square.
Differences between sample means were assessed using Student’s paired t-test. Data are M±m, with M the group mean and m its error. Non-normally distributed variables were described nonparametrically using median and 25th and 75th quartiles. Before–after changes were assessed by the paired Wilcoxon method. Significance was p<0.05 [13].
Results and discussion
Combined hypoxic and oxygen therapy improved every part of the respiratory functional system. Significant increases occurred in tidal volume, 13.25±1.01%; minute ventilation, 11.54±1.03%; alveolar ventilation, 15.27±1.02%; vital capacity, 12.5±0.02%; and forced expiratory volume, 12.1±0.2%.
Circulation improved: heart rate fell significantly from 86.4±0.16 to 75.3±0.14 beats/min, while stroke volume increased 13.17±1.06 mL. Together these produced a 12.34±1.26% rise in cardiac output (p<0.05), attributed to increased coronary flow and myocardial contractility. Normalised pulmonary ventilation, perfusion and diffusion raised SaO₂ from 95.4±0.02% to 98.5±1.01%. Greater tissue oxygen extraction increased the arterial–venous oxygen-tension difference and oxygen-consumption rate by 21.4±2.3%.
Haemoglobin rose from 123.5±2.18 to 145.8±3.27 g/L, with oxygen capacity rising significantly from the source-reported 176.6±2.18 g/L to 195.41±2.1 mL/L. This was attributed to hypoxia-inducible factor 1, HIF-1, released during IHT hypoxia, in agreement with the literature [14, 15].
Systolic and diastolic pressure fell significantly. Office measurements in 115 patients improved. Ambulatory monitoring showed lower 24-hour systolic, diastolic and mean pressure and heart rate, as well as lower systolic and diastolic area and time indices. Pressure variability was unchanged (Table 1).
By time of day, significant reductions in systolic, diastolic and mean pressure, systolic and diastolic time and area indices, and heart rate occurred during wakefulness (p<0.05). No blood-pressure changes occurred during sleep. The combination therefore worked best during daytime wakefulness, when sympathetic activity rises. The comparison group showed no significant changes.
Electrocardiography and echocardiography
ECG abnormalities included lower T-wave amplitude in V3–V5 in 15%, ST displacement over 1 mV in V3–V5 and coronary-type T waves in I, aVL, V3 and V4 in 32%, indicating hypoxic myocardial injury. Sinus tachycardia occurred in 85%, supraventricular arrhythmias in 51% and ventricular arrhythmias in 12%. Dystrophic myocardial changes produced electrical instability and greater sensitivity to stimuli, increasing the likelihood of ectopic hyperexcitable foci causing supraventricular and ventricular extrasystoles, atrial fibrillation and flutter, and paroxysmal tachycardia.
Increased excitability was reflected by atrial extrasystoles in 46% and isolated ventricular extrasystoles in 16%. In 26%, QRS exceeded 0.12±0.01 seconds, T waves were negative in V1, V2 and aVR and positive in I, V5 and V6. These were interpreted as incomplete right bundle-branch block and impaired conduction. PR exceeded 0.21±0.01 seconds without dropped ventricular complexes in 25%, indicating first-degree AV block; second-degree AV block occurred in 14%. Fifteen percent showed early left ventricular hypertrophy, the principal myocardial response to increased peripheral resistance. Loading activates gene-expression changes in contractile proteins, increased sympathetic and renin–angiotensin tone and secondary aldosteronism, promoting hypertrophy.
ECG signs included longer QRS, deeper S in V1–V2, higher R in V5–V6 and left-axis deviation.
Echocardiography found no cardiac injury in 35% and hypertrophic remodelling with preserved left ventricular diastolic function in 45%. Arrest of hypertrophic remodelling and left ventricular hypertrophy progression was an important treatment result.
Hypoxic plus oxygen therapy reduced excitability, with fewer ventricular and supraventricular extrasystoles attributed to blocked ectopic impulse-generating foci. Sinus rhythm normalised and sinus tachycardia episodes declined. N.R. Prabhakar’s work [15] showed that long-term hypoxic adaptation promotes angiogenesis and coronary dilation, increasing coronary flow and myocardial oxidative phosphorylation. This reduces dystrophic changes and was reflected in our findings. Treatment also accelerated conduction, with fewer bundle-branch, sinoatrial and AV blocks on ECG.
Oxidative stress and lipids
Treatment enhanced antioxidant activity and suppressed oxidative lipid and protein destruction. Malondialdehyde fell to 65.48 (44.7–75.14) μmol/L (p<0.05), reducing radical damage to membranes and organelles. Comparisons showed no significant change. Glutathione peroxidase and SOD activity rose significantly (Table 2).
Combined treatment effectively suppressed oxidative stress in hypertension. Lower peroxide compounds and stronger enzymatic antioxidants suppressed lipid and protein peroxidation in the vascular wall and endothelium and contributed to blood-pressure normalisation.
Reduced oxidative stress improved the lipid profile. Total cholesterol fell from 7.2±0.13 to 5.4±0.06 mmol/L and triglycerides from 3.25±0.04 to 2.15±0.01 mmol/L (both p<0.05). HDL rose from 0.75±0.01 to 1.01±0.01 mmol/L (p<0.05), while LDL fell from 7.4±0.01 to 3.62±0.02 mmol/L (p<0.05) and VLDL declined, reducing the atherogenic coefficient. Comparisons showed no significant changes. Lower total cholesterol, LDL and VLDL with higher HDL significantly reduced blood atherogenic potential and the risk of progressive atherosclerotic vessel injury and hypertension.
These changes allowed lower doses of baseline antihypertensives: ACE inhibitors, angiotensin II receptor blockers, diuretics, central and peripheral beta blockers, and slow calcium-channel inhibitors. This matters because hypertensive patients require continuous medication owing to high complication risk.
Conclusions
Combining IHT with oxygen cocktails normalised every stage of the functional system, improving oxygen supply through external respiration, circulation, blood oxygen transport and tissue consumption.
The studies provide a pathogenetic rationale for normobaric IHT combined with oxygen cocktails in hypertension. Hypoxic plus enteral oxygen therapy mobilises adaptive mechanisms and reduces hypoxaemia and tissue hypoxia by improving oxygen transport at every stage.
Table 2. Oxidative stress before and after combined treatment, n=115
| Stage | Malondialdehyde, μmol/L | Glutathione peroxidase, μmol/g Hb/min | SOD, activity units/g Hb |
|---|---|---|---|
| Before | 105,4 (67,5–115,5) | 48,4 (45,1–68,4) | 2,9 (2,12–3,47) |
| After | 65,48 (44,7–75,14)** | 99,72 (77,4–153,2)** | 4,06 (3,02–5,78)* |
Median, 25th and 75th quartiles. * p<0.05; ** p<0.01 versus baseline.
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Full main-text translation of: Ашагре Сарон Мерша, Борукаева И.Х. Патофизиологическое обоснование применения интервальной гипокситерапии и энтеральной оксигенотерапии в лечении гипертонической болезни. Кабардино-Балкарский государственный университет им. Х.М. Бербекова, Нальчик.
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