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Biomedical subjects

M M Mirrakhimov

Publications and source records attributed to M M Mirrakhimov.

At least 19 recordsLinked to original sources
PubMed2001

Sildenafil inhibits hypoxia-induced pulmonary hypertension.

BACKGROUND: This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice. METHODS AND RESULTS: In a randomized, double-blind study, sildenafil 100 mg or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11% O(2) for 30 minutes. Pulmonary artery pressure (PAP) was measured with an indwelling right heart catheter. The acute 56% increase in mean PAP produced by hypoxia during placebo treatment (mean PAP [mean+/-SD mm Hg]: normoxia 16.0+/-2.1 versus hypoxia 25.0+/-4.8) was almost abolished by sildenafil (normoxia 16.0+/-2.1 versus hypoxia 18.0+/-3.6), with no significant effect on systemic blood pressure. In the isolated perfused lung of wild-type and endothelial nitric oxide synthase (eNOS)-deficient mice, sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction. Wild-type mice dosed orally with the drug (25 mg. kg(-1). d(-1)) throughout 3 weeks of exposure to hypoxia (10% O(2)) exhibited a significant reduction in right ventricular systolic pressure (placebo versus sildenafil: 43.3+/-9.9 versus 29.9+/-9.7 mm Hg, P<0.05) coupled with a small reduction in right ventricular hypertrophy and inhibition of pulmonary vascular remodeling. In eNOS mutant mice, sildenafil attenuated the increase in right ventricular systolic pressure but without a significant effect on right ventricular hypertrophy or vascular remodeling. CONCLUSIONS: Sildenafil attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a novel approach to the treatment of this condition. The eNOS-NO-cGMP pathway contributes to the response to sildenafil, but other biochemical sources of cGMP also play a role. Sildenafil has beneficial pulmonary hemodynamic effects even when eNOS activity is impaired.

Adolescent↗
PubMed2001

Changes in surface charge of low-density lipoproteins during oxidative modification.

The negative surface charge of low-density lipoproteins increased during their oxidative modification induced by autooxidation at 37 degrees C. The degree of changes depended on the time of autooxidation: the surface charge remained practically unchanged after short-term oxidation (6-h incubation), but then progressively increased and after 24-h oxidation it 2-fold surpassed the initial level. Long-term incubation of low-density lipoproteins in the presence of EDTA inhibiting lipid peroxidation did not change their surface charge. These changes probably contribute to atherogenic activity of oxidized low-density lipoproteins. The degree of oxidative modification of low-density lipoproteins was precisely estimated using fluorescence probes.

Anions↗
PubMed2000

The quality of sleep and periodic breathing in healthy subjects at an altitude of 3,200 m.

The medical risks of travel and stay at high altitude are well known. Many more people travel for recreation to lower but still significant altitudes. To investigate the quality of sleep and sleep-related breathing disorders (SRBD) at that altitude we performed full polysomnography in nine young volunteers at lowland (760 m above sea level) on the first and sixth night after ascent to 3,200 m. There have been few studies on such populations. The subjects were nonsmoking healthy males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. Although there was no statistically significant difference in the duration of stages and sleep quality between low altitude night and both nights at high altitude as assessed by percent of sleep spent in stage 1, 2, 3+4 NREM, and REM sleep, total sleep time (TST), and sleep efficiency; the number of arousals and awakenings doubled at high altitude. There was no periodic breathing (PB) during sleep, except in isolated central events of SRBD, at low altitude. PB appeared at altitude mostly during NREM sleep and its intensity remained stable throughout the study period. Individual variations of PB intensity were high, ranging from 0.1 to 24% of TST. There were also some episodes of obstructive apnea and hypopnea during sleep at high altitude (p < 0.001). Mean SaO2 was lower during the study nights at high altitude when compared with low altitude. There were some signs of ventilatory acclimatization as shown by a higher mean SaO2 during the sixth compared with the first night at altitude (p < 0.001). We conclude that the sleep quality at the altitude of 3,200 m remains satisfactory when compared to low altitude. There is high individual variability in intensity of PB at that altitude.

Acclimatization↗
PubMed1999

[Quality of sleep and periodic breathing in healthy individuals working at an altitude of 3700 meters].

We performed full polysomnography (PSG) in 7 healthy miners of Kyrghyz origin (mean age 25 +/- 6 years) working in 2 weeks shifts at Kumtor gold mines at the elevation of 4200 m. They slept in comfortable dormitories situated at 3700 m. To avoid acute mountain sickness all subjects received acetazolamide 3 x 0.25 daily during 2 days preceding ascent and during 2 days at altitude: PSG was performed three times: at 760 m (1) and on the 1st (2) and 7th night (3) after rapid ascent (aircraft) to high altitude using SomnoTrac 4250 sleep laboratory. We found that sleep efficiency was good at lowland and in the mountains averaging 81.79% and 84% respectively. Although there were no significant differences in percentage of sleep stages and of total sleep time between lowland and both nights at high altitude, arousals and awakenings were more frequent in the mountains. Episodes of periodic breathing (PB) appeared at high altitude. There was a large individual variability in PB on both nights at altitude. The time spent in PB ranged from 4 to 30 minutes during the first night at altitude and from 3 to 17 minutes during the second one. PB appeared mainly during non-REM sleep and aggravated arterial blood desaturation.

Adult↗
PubMed1998

[Three week stay at a height of 3700-4200 m. causes mild pulmonary hypertension in healthy men].

High altitude hypoxia leads to development of hypoxic pulmonary hypertension. We studied 27 healthy caucasian subjects aged 24 to 59 years, mean 41.6 +/- 9 y, working on 4 week shifts at the Kumtor gold mines at the altitude of 3700-4200 m. Pulmonary circulation was studied twice by Echo-Doppler using Toshiba SSD-160. The first investigation was performed at the level of 730 m at the end of 4 week holiday spent in the lowland, the second investigation on the 23rd day at altitude. Pulmonary artery acceleration time decreased from 131 +/- 14 ms to 105 +/- 14 ms (p < 0.001). Calculated pulmonary arterial mean pressure increased from 15.1 +/- 2 to 25.4 +/- 8 mmHg (p < 0.001). Right ventricular preejection period increased from 93 +/- 14 to 102 +/- 19 ms (p < 0.05). Other echo variable did not change. We conclude that healthy subjects submitted to 3 week exposure to high altitude hypoxia (oxygen pressure in the inspired air 82-88 mmHg), developed mild pulmonary hypertension, regressing after recovery at the lowland.

Adult↗
PubMed1996

[The rehabilitation under alpine conditions of the participants in the cleanup of the accident at the Chernobyl Atomic Electric Power Station who are ill with chronic bronchitis].

24 patients exposed to low-dose radiation after the Chernobyl accident were examined before and after 24-day treatment of chronic bronchitis in the high-altitude rehabilitation center (3200 m above the sea level) in Tien Shan. Sanogenic alpine climate improved the patients' general condition, physical performance and lung ventilation, corrected compromised immunity. After high-altitude adaptation tracheobronchial inflammation alleviated, cytologic composition and surface activity of bronchoalveolar fluid returned to normal. Therefore, high-altitude treatment of Chernobyl accident victims with chronic bronchitis is effective and can be recommended for such patients.

Adaptation, Physiological↗
PubMed1996

[Periodic breathing during sleep at high altitudes in patients with bronchial asthma].

Earlier we found that asthmatic patients treated at a high altitude sanatorium (3.200 m) had numerous episodes of arterial blood desaturation during the night. To investigate if periodic breathing (PB) was responsible for those episode we studied 5 asthmatics (A) (mean age 34 yrs) and 3 healthy controls (C) (mean age 28 yrs) using MESAM 4, a simple, portable system recording breathing sounds, heart frequency, arterial blood saturation and body position. A and C subjects were first investigated at low altitude (760 m). There was no PB at 760 m in either group. At high altitude MESAM 4 recordings were performed on the 2nd and the 7th night after the ascent. On the 2nd night in the A group subjects the number of PB cycles averaged 37.2 (22-54) occupying 3.2% (2-5%) of estimated sleep time. The number of no-PB episodes was 52.4 (23-109). In the C group subjects the number of PB cycles was 83.6 (10-147) occupying 9% (1-14%) of estimated sleep time. The number of no-PB episodes averaged 45.6 (6-84). On the 7th night in A the number of PB cycles was 46.6 (15-69) occupying 4% (1-7%) of estimated sleep time. The number of no-PB was 54.8 (13-147). In C the number of PB cycles averaged 29.3 (12-59) occupying 3.3% (2-6%) of estimated sleep time. The number of no-PB was 20.3 (9-37). We conclude that majority of desaturations during sleep in asthmatics at altitude of 3.200 m was not related to PB; the mechanisms of these desaturations require more investigations.

Adult↗
PubMed1996

[Quality of sleep and periodic breathing during sleep in healthy persons at a height of 3200 meters].

In order to investigate quality of sleep and sleep-related breathing disorders (SRBD) at high altitude we performed full polysomnography in 9 young healthy volunteers at lowland (760 m above see level) and on the 1st and 6th night after the ascent to the altitude of 3200 m. The subjects were non-smoking males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. We found no statistical difference in sleep quality between low and both nights at high altitude as considered by % of stages 1, 2, 3 + 4 non-REM, and REM sleep, total sleep time, sleep efficiency, and number of awakenings+arousals. There was no periodic breathing (PB) during sleep but some central events of SRBD at low altitude. PB appeared at high altitude mostly during non-REM sleep and remained stable throughout the study period. There were also some obstructive SRBD found during high altitude nights. Mean SaO2 was lower during both nights at high altitude when compared to low altitude (p < 0.00001). It was higher during the 6th than during the 1st night at altitude (p < 0.0001). Minimum SaO2 was comparable during low altitude and 6th night at altitude and was lower during the 1st altitude night (p < 0.02). We conclude that sleep quality at the altitude of 3200 m remains unchanged when compared to lowland. There is high individual variability in PB at altitude and its intensity is negligible.

Adult↗
PubMed1996

[Effect of altitude on blood oxygenation during sleep in patients with bronchial asthma].

The aim of our study was to investigate the severity of overnight arterial blood desaturations in patients with asthma at the altitude of 3200 meters above sea level. 12 asthmatics and 12 healthy controls were investigated. Three overnight pulsoximetries were performed in all subjects, one at the lowland and on the 1st and 5th night at the altitude. Mean SaO2 at the lowland was significantly lower in asthmatics than in the controls (p < 0.01). After the ascent to high altitude severe fall in mean SaO2 was noted in both groups (from 94.3% to 85.8% in asthmatics and from 97.1% to 88.7% in controls) (p < 0.001 for both groups). After few days of acclimatization mean SaO2 rose to 88.8% in asthmatics and to 91.3% in controls, but was still significantly lower than at the lowland (p < 0.001 for both groups). At the altitude differences in mean SaO2 between two groups were not statistically significant. We conclude that severity of overnight desaturations at high altitude do not vary between asthmatics with impaired respiratory function and healthy subjects.

Adolescent↗
PubMed1994

[The clinico-functional characteristics of pulmonary arterial hypertension in systemic scleroderma].

Electro-, phono-, echo-, and Doppler echocardiography, bulbar biomicroscopy were performed in 54 SS patients aged 18-64. Mean pulmonary arterial pressure (PP) was determined at Doppler echocardiography on Toshiba SSH-40A unit according to techniques developed by M. M. Mirrakhimov et al. in 1989. The diagnosis of pulmonary hypertension (PH) was made in PP above 18 mm Hg. A close relationship was found between SS history and PH registration. With growing SS duration, PH severity increases, microcirculatory disorders progress. Main PH risk factors in SS patients are believed SS duration, activity, Raynaud's syndrome presentation. Doppler echocardiography can effectively diagnose PH in its subclinical stage, is noninvasive.

Adolescent↗
PubMed1993

[Painless ischemia in the acute period of myocardial infarct].

The examination of 119 patients with primary acute macrofocal myocardial infarction included 24-hour monitoring to detect episodes of painful or painless ischemia. Three groups of patients were identified: 55 subjects with both painful and painless ischemia, 39 subjects with painless ischemia and 25 patients without ischemia. Diastolic and systolic functions of the left ventricle were assessed at Doppler echocardiography in all the patients who were followed up for 1 year. It was found that painless ischemia revealed early in myocardial infarction affects negatively left ventricular systolic and diastolic functions thus strongly suggesting an unfavorable short-term prognosis.

Acute Disease↗
PubMed1992

New approaches to noninvasive assessment of pulmonary artery pressure.

Direct measurement of pulmonary artery pressure (PAP) was performed in 36 patients; right ventricular (RV) isovolumic relaxation time (IRT) and RV systolic output acceleration time (AcT) values were assessed by pulsed Doppler and 2-M echocardiography. There was a fairly good correlation between RV IRT and systolic PAP (r = 0.898; SEE = 7.8 mmHg) and a somewhat weaker one between RV AcT and systolic PAP (r = -0.880; SEE = 8.37 mmHg). Correlation coefficients were the highest between systolic PAP and the [formula: see text] (r = 0.972; SEE = 4.14), and also between mean PAP and the 10-RV AcT/100 predictor: y = 158x + 6.7 (r = 0.951; SEE = 3.48 mmHg). With +/- 5 mmHg deviations, systolic PAP measurements were accurate in 78% and those of mean PAP in 98% of the patients. The double-blind assessment of the reproducibility of the suggested noninvasive PAP measurement was performed in 18 subsequent patients; the interstudy variability of the measurement was 0.88 +/- 0.94 mmHg and 1.22 +/- 1.23 mmHg (p > 0.05), whereas interobserver variability was 1.90 +/- 1.70 mmHg and 1.67 +/- 1.63 mmHg, respectively (p > 0.05). Thus, a combined use of the most informative intervals of RV cycle--IRT and AcT--contributes to the accuracy of noninvasive PAP measurement.

Adolescent↗
PubMed1992

[Functional morphology of resistant pulmonary vessels and capillaries in individual and species adaptation to high altitude].

Morphological and structural rearrangement of resistant pulmonary vessels and alveolar capillaries was assessed in lowland animals (rabbits) during high-altitude adaptation, in aboriginal high-altitude species (yaks, mountain goats) and on native highlanders. Structural adaptive developments in pulmonary vessels and capillaries of high-altitude animals contribute to maximal facilitation of gas diffusion. Similar adaptive changes in pulmonary resistant vessels and capillaries of laboratory animals and in native highlanders are associated with pathological alterations manifest in the elevation of pulmonary vascular resistance, right ventricular hypertrophy, increases in the thickness of the basal membrane of the air-blood barrier. In all the subjects studied the process of high-altitude adaptation is associated with hypertrophy of pulmonary endothelium. The intensification of pulmonary endothelium. The intensification of pulmonary endothelium metabolic activity may be directed at regulation of vascular tone.

Adaptation, Physiological↗
PubMed1992

[The treatment of hypertension by adaptation to high-altitude hypoxia].

Ethnically close male populations aged 30-59 years who reside in high mountains (2800-3600 m above the sea level) and in low lands (800-900 m above the sea level) of the Tien Shan and the Pamirs were screened. The incidence of essential hypertension was found to be significantly lower (4.2%) among the highlanders than in the lowlanders (15.4%). In highlanders, hypertension is characterized by a high concurrence with high-altitude arterial hypertension and right ventricular hypertrophy. Daily urinary aldosterone excretion is substantially lower in residents of high mountains and natriuresis is higher than that in those from low-lands. Sixty-eight patients with mild hypertension took daily treatment as pressure chamber uplifting (3200 m above the sea level; pO2 112 mm Hg) for 15 days and 45 patients with moderate hypertension were treated with medium-land (1600 m; pO2 134 mm Hg) adaptation for 24 days. Pressure chamber hypoxic training and medium-land adaptation in 69% of patients with mild hypertension and 64.4% with moderate hypertension without signs of target organ lesions produced steady antihypertensive effects, a steady-state (for a 1.5-year follow-up) decrease in cardiac mechanical work, peripheral vascular resistance, arterial impedance, and an improvement of physical fitness. It was proposed to use hypoxic (pressure chamber and high-altitude) training for the treatment of early hypertensive disease and its secondary prevention.

Adaptation, Physiological↗
PubMed1992

[The effect of altitude factors on the human body].

Negative consequences of the impact of alpine factors on the body of man are described. Alpine acute lung edema is one of the dangerous diseases that may develop under alpine conditions. This may affect not only beginners but also aborigines of the mountains, who return to the places they come from after a temporary stay in lowlands. Acute brain edema is regarded as no less severe condition. It may occur in about 1.2% of the people who climb to a height of 4500-5000 m. Primary alpine pulmonary arterial hypertension and chronic alpine cor pulmonale are fairly prevalent under alpine conditions.

Acute Disease↗