[Adaptation to hypoxia and ischemic preconditioning: from basic research to clinical practice].

Experimental and clinical studies of the last ten years gave evidence of successful application of the protective effect of hypoxia in clinical practice. The view of hypoxia as an exclusively injurious factor has undergone significant changes. A promising approach to solving the problem of heart adaptation to ischemic injury is the use of cellular mechanisms realized through myocardial ischemic preconditioning (IP). Modern understanding of the mechanisms of IP protective effect takes into consideration the processes underlying the development of adaptation to hypoxia related to the changes in intracellular metabolism and accompanied by a stronger activation of the systems responsible for adaptation. All this provides a real opportunity for studying intracellular functional and metabolic mechanisms of adaptation to hypoxia and ischemia, formation of adaptive syndromes in clinical practice, development and implementation of new evidence-based medical technologies for diagnostics, prevention, and rehabilitative treatment of heart pathology.

[Cardioprotective capabilities of drug meldonium in secondary prevention after percutaneous coronary intervention in patients with documented myocardial ischemia].

The purpose of research ­ analysis of capabilities in cytoprotective drug mеldonium, in complex in the cardioprotective effect of secondary prevention after percutaneous coronary intervention (PCI). Patients with stable coronary heart disease (n=35 ) aged ≤65 years with incomplete revascularization at 6 months after PCI and positive exercise test (SFI) were randomized 1:1 to groups controlled physical training (CPT) with intensity 80% and a duration of 2 weeks (10 SFI): group 1 (n=17; 53,9±6,2 years) and group 2 (n=18; 56,1±4,8 years). Patients in Group 1, in addition to SFI mеldonium administered at a dose of 1000 mg/ml intravenously. In the 1st group on the background mеldonium adjunctive therapy showed a significant increase in the duration from 15±2 to 32±7 min for the 10th CPT (p<0.05). Index of maximum oxygen consumption after 10 intense CPT increased to 20.8±1.06 ml/kg/min compared to baseline (18.6±1.1 ml/kg/min, p<0.05) and the control group (18.5±1.5 ml/kg/min, p<0.05). Use of meldonium was also associated with decrease of maximum ST-segment depression (from -0.18±0.1 to 0.10±0.2 mV), increases of exercise duration (from 364±22 to 556±29 s) threshold heart rate (from 118±12 to 132±5 bpm), decrease of time of ST segment recovery to baseline (from 385±32 to 242±22 s, p<0.05). Final level of free fatty acids in the meldonium group was significantly lower than that in the control group (0.248±0.047 vs. 0.265±0.031 mg/dl). Inclusion of meldonium in complex treatment after PCI potentiates cardioprotective effect of intensive CPT as evidenced by the positive dynamics of ECG and biochemical markers of myocardial ischemia.

[Approaches potentiating cardioprotective effect of ambulatory physical training in patients with ischemic heart disease and multivessel coronary artery involvement after coronary stenting].

Cardiorehabilitation of patients with multivessel coronary lesions is an obligatory component of ambulatory stage of care. With the aim of potentiating cardioprotective and antiischemic impact of rehabilitative preventive measures in 36 patients with ischemic heart disease (IHD) and multivessel coronary artery involvement who had undergone percutaneous coronary intervention we studied cardioprotective and antiischemic effect of long-term (24 weeks) administration of 70 mg/day trimetazidine in combination with moderate intensity physical training with the use of distance surveillance by a physician. The chosen therapeutic approach in patients with residual ischemia after incomplete anatomical revascularization provided early persistent formation of cardioprotective and antiischemic effect proven by increase of tolerance to physical exercise, improvement of diastolic function, and positive dynamics of both ECG parameters and biochemical markers of myocardial ischemia.

[Possibilities of improvement of prognosis in patients with type 2 diabetes mellitus after coronary interventions].

We present results of investigation of fenofibrate in patients with ischemic heart disease and type 2 diabetes mellitus after myocardial revascularization at various terms of its administration. We have shown its efficacy in correction of diabetic dyslipidemia, positive influence on clinical status and long term result of coronary intervention. We have established that early (first 7 days) prescription of fenofibrate - Tricor to patients with ischemic heart disease and type 2 diabetes mellitus after myocardial revascularization lowers number of diagnostic coronary angiograms and repeat percutaneous coronary interventions by 11% during first year of follow-up.

[Functional screening test for latent arterial hypertension detection in young patients].

We assessed diagnostic value of acute-hypoxia test (AHT) for detection of latent arterial hypertension in 317 young persons from different social groups (mean age 25.6+/-5.1 yrs) without clinical signs of cardiovascular diseases. We performed AHT and ambulatory blood pressure monitoring (ABPM). Sensitivity and specificity of AHT for detection `of latent arterial hypertension were 97.9 and 94.7%, respectively. Agreement of results of AHT and ABPM was 79.6% in patients with high normal blood pressure (BP) and 100% in patients with BP >140/90mm Hg. The test was safe and its results were highly reproducible.

[Rehabilitative and prophylactic measures including physical training for the correction of risk factors in patients presenting with ischemic heart disease following percutaneous coronary interventions].

The authors report the results of analysis of effectiveness of active rehabilitative and prophylactic measures undertaken at the outpatient treatment stage including long-term controlled physical training of moderate intensity in patients presenting with coronary heart disease following percutaneous coronary interventions. The emphasis was laid on the possibility to prevent traditional risk factors of cardiovascular diseases. It was shown that the proposed approach allows a few risk factors (dyslipidemia, hypodynamia, arterial hypertension, smoking, and obesity) to be simultaneously corrected.

[Novel approaches to assessment of rehabilitative-preventive quality measures in patients with ischemic heart disease].

Cardiorehabilitation and secondary prevention in patients with ischemic heart disease (IHD) are at present actively introduced in practical health care. However problems of standardization of methods of cardiorehabilitation and secondary prevention remain unsolved and criteria of efficacy of conducted measures in patients with IHD have not been elaborated. On the basis of analysis of clinical status, physical working capacity, blood pressure dynamics, lipid spectrum, smoking, body mass index, and quality of life of patients we have created a set of clinical indicators of efficacy of rehabilitative-preventive aid which will allow to present all components of efficacy at the level of conduction of clinically proven measures.

[Physical training at ambulatory-polyclinical stage in complex rehabilitation and secondary prevention of patients with ischemic heart disease after acute incidents. Effect on physical working capacity, hemodynamics, blood lipids, clinical course and prognosis (Russian cooperative study)].

AIM: To investigate efficacy of early and long term physical training (PT) of moderate intensity in conditions of practical health care in Russia in patients with ischemic heart disease (IHD) of able to work age - survivors of acute coronary events. MATERIAL AND METHODS: Three hundred ninety two patients were enrolled in this study. They were randomized into intervention group " O" (n=197) and control group " C" (n=195). Inclusion period was 3- 8 weeks from onset of myocardial infarction (MI), unstable angina (UA), or intervention on coronary arteries. Patients were followed up for 1 year and efficacy of intervention was assessed by results of laboratory (levels of lipids), instrumental (ECG, exercise test on veloergometer, echocardiography), and clinical examination. In the group " O" regimen of PT with work loads of moderate intensity (50-60% of power achieved during exercise test) was used. Duration of FT was 45 - 60 min, frequency - 3 times a week. All patients received standard therapy for IHD and a lipid lowering drug when indicated. RESULTS: Proofs of efficacy of PT in the given contingent of patients were obtained. This was manifested by significant increase of physical working capacity: prolongation of exercise time (+31.7%, p<0.001), increases of volume of work performed (+74.3%, p<0.001) and efficiency of cardiac work according to results of exercise tests. All parameters were significantly different from those in the group " C" . Structural functional parameters of the heart also improved in the group " O" : left ventricular (LV) stroke volume increased 4.5% (p<0.005), ejection fraction increased 7.2% (p<0.001), diastolic LV volume decreased 2.5% (p<0.05), systolic LV volume decreased 8.1% (p<0.001). In the group " C" stroke volume and LV ejection fraction rose to a lesser degree - by 5.5% (p<0.01) and 2.9% (p<0.05), respectively. Differences between groups in dynamics of these parameters turned out to be significant (p<0.05). Moreover in group " C" LV diastolic volume increased 2.3% (p<0.05) and systolic volume did not change, while left atrium increased 3.4% (p<0.002). At intergroup comparison differences in dynamics of these parameters were significant (p<0.005). Analysis of lipid profile after 1 year showed no changes in patients of group " C" , while in group " O" it revealed significant (3.6%) lowering of total (T) cholesterol (CH) (p<0.05 compared with baseline and change in group " C" ) and elevation of high density lipoprotein (HDL) CH (+12.3%, p<0.001; compared with group " C" p<0.005). Atherogeneity index TCH/HDLCH decreased 8.5% in the group " O" (p<0.01), and increased 12% (p<0.02) in the group " C" , difference between groups was statistically significant (p<0.001). In the group " O" body mass index decreased 2.8% (p<0.001), and frequency of attacks of angina decreased 50.8% (p<0.001; compared with group " C" p<0.001). Statistically significant differences were registered between the following parameters of composite end point and surrogate points: total number of cardiovascular events - 26 (14.8%) vs 47 (27%), p<0.01; number of cardiovascular catastrophes - 5 (3%) vs 15 (8.7%), p<0.05; number of days out of work because of exacerbation of IHD per 1 person/year - 2.4 vs 4.2, p<0.05 in groups " O" and " C" , respectively. Thus in the group " O" positive effect of PT on the course and outcomes of the disease was registered compared with the group " C" . CONCLUSION: The data obtained are indicative of sufficient efficacy of the used program of PT and feasibility of its application in practice of ambulatory rehabilitation of patients with IHD - survivors of acute coronary events. It also can be looked upon as a method of secondary prevention as results of the study showed its positive impact on risk factors and outcomes of the disease.

[Exercise in outpatient complex rehabilitation and secondary prophylaxis in patients with ischemic heart disease after acute coronary events (a cooperative trial in Russia)].

AIM: To assess efficacy of early and long-term exercise in patients with ischemic heart disease (IHD) after acute coronary events (acute myocardial infarction--AMI, unstable angina--UA, coronary artery bypass grafting--CABG) in wide outpatient medical practice of Russia. MATERIAL AND METHODS: Three to eight weeks after the acute coronary event (ACE) 373 patients from different clinics of RF regions were randomized into two groups: the study group (n = 188) and a control one (n = 185). Both groups received standard therapy, the study group performed also a special exercise program (moderate exercise for maximum 1 hour 3 times a week for a year). The efficacy of the treatment was assessed by clinical, device and biochemical findings during 6-month follow-up. RESULTS: Physical work capacity, total amount of performed work (PW) in stress test rose in the study group by 26.5% (p < 0.01) and 59.4% (p < 0.01), respectively; HRmax and BPSmax x HRmax increased by 6.4 and 9.8%, respectively, p < 0.01); PW/Hrpeak rose by 48.6% (p < 0.01), PW/DP peak--by 45.9% (p < 0.01). Left ventricular ejection fraction increased by 5.6% (p < 0.05), LV stroke volume--by 3.4% (p < 0.05). In 6 months, controls demonstrated a 4.7% (p < 0.05) rise in HDLP cholesterol, total cholesterol lowered in the study group by 6.4% (p < 0.01), body mass index--by 1.9%, number of anginal attacks--by 0.9%. CONCLUSION: The proposed exercise program is effective and can be applied in outpatients after acute coronary events. The program can be also used as a method of secondary prophylaxis as it lowers total cholesterol, atherogenic index and body mass index.

[Correction of NO-dependent cardiovascular disorders by adaptation to hypoxia]. / Korrektsiia NO-zavisimykh serdechno-sosudistykh narushenii s pomoshch'iu adaptatsii k gipoksii.

Spontaneously hypertensive rats (SHR-SP) were adapted to intermittent hypobaric hypoxia in an altitude chamber for 40 days. The adaptation to hypoxia prevented an excessive endothelium-dependent relaxation and hypotension characteristic of myocardial infarction. The adaptation also attenuated the increase in blood pressure and prevented impairment of the endothelium-dependent relaxation in SHR-SP. The universal nature of the adaptation allows to use it for correcting many cardiovascular disorders related to diverse alterations of NO metabolism.

[The role of preventing nitric oxide deficiency in the antihypertensive effect of adaptation to hypoxia]. / Rol' preduprezhdeniia defitsita oksida azota v antigipertenzivnom éffekte adaptatsii k gipoksii.

Shortage of endothelial nitric oxide (NO) manifested as decreased daily urinary excretion of nitrate and nitrite as well as attenuated endothelium-dependent relaxation of conduit and resistance vessels progresses with age-related increase of blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Simultaneous NO-dependent suppression of vascular contractions is, apparently, due to the inducible NO synthase activity in vascular smooth muscle specific for spontaneously hypertensive rat. Adaptation of rats to hypobaric hypoxia initiated at early hypertensive stage (at the age of 5-6 weeks) decelerates hypertension progress. The antihypertensive effect of the adaptation was accompanied by stimulation of endothelial NO synthesis and prevention of impaired NO-dependent response in isolated blood vessels. Nitric oxide stores were formed in the vascular wall of SHRSP and WKY rats at the same time. The obtained data indicate a significant role of correction of endothelial NO deficiency in the antihypertensive effect of adaptation to hypoxia.

[Effects of stress and exercise tests on the functional state of cardiac performance and the state of adrenergic regulation in patients with ischemic heart disease]. / Vliianie stressornoi i fizicheskoi nagruzok na funktsional'noe sostoianie serdechnoi deiatel'nosti i sostoianie adrenergicheskoi reguliatsii u bol'nykh ishemicheskoi bolezn'iu serdtsa.

In patients with coronary heart disease, stress was found to provoke both ischemic and arrhythmic responses. As compared with exercise test, stress caused arrhythmic reactions more frequently than ischemic ones. Stress was ascertained to provoke ischemic and arrhythmic reactions mainly via increased cardiac function. It also affected the myocardium and coronary bed by the direct action of catecholamines and other stress hormones.

[Significance of visual-scanning Doppler detection in the diagnosis of early stages of cardiac insufficiency in patients with ischemic heart disease]. / Znachenie vizual'no-poiskovoi dopplerovskoi lokatsii v diagnostike rannikh stadii serdechnoi nedostatochnosti u bol'nykh ishemicheskoi bolezn'iu serdtsa.

A method was developed for visual monitoring myocardial structures in the mode of continuous Doppler location by using a commercial Soviet device. The method proposed measures the velocity of mobility of well-defined cardiac structures. Clinical examinations showed that myocardial contractile abnormalities could be detected earlier by visual-prospecting Doppler echocardiography than by routine Doppler location and echocardiography. The IVth standard location position is the most informative in the detection of impaired contractility. When the Doppler echocardiogram in the first additional position is analyzed, the appearance of P wave may serve as a reliable criterion for diminished myocardial contractility.

[Effects of stress and exercise on rhythm activity of the heart and state of adrenergic regulation in patients with neurocirculatory dystonia]. / Vliianie stressornoi i fizicheskoi nagruzok na ritmicheskuiu deiatel'nost' serdtsa i sostoianie adrenergicheskoi reguliatsii u bol'nykh neirotsirkuliatornoi distoniei.

Responses of healthy subjects and patients with a cardiac type neurocirculatory dystonia (NCD) to exercise and stress were evaluated. Stress was ascertained to cause a higher enhancement of catecholamine excretion than exercise. In patients with NCD, resting adrenaline (A) excretion was increased by 50%, whereas the noradrenaline (NA) one remained unchanged. The A/NA ratio showed a more than 1.5-fold increase. A stress-induced rise in NA excretion was 4 times higher in NCD patients than in healthy subjects. In the patients, resting dopamine (D) excretion was lower and the D/A + NA ratio was decreased both at rest and during exercise. In NCD the higher adrenergic response to stress was followed by the occurrence of arrhythmias in more than a half of the patients. The healthy subjects and the patients with NCD developed no arrhythmias during exercise. It has been suggested that changes in adrenergic control and associated arrhythmias are caused by dysfunction of the stress-limiting systems in NCD.