Association of Regulatory and Adaptive Status in Humans with Serotonergic Transmitter System Gene Polymorphism.

The regulatory and adaptive status was determined in 202 healthy subjects by the parameters of the cardiorespiratory synchronism probe. We performed molecular-genetic analysis of polymorphic variants of the main gene of serotonin biosynthesis, tryptophan hydroxylase TPH1 (A218C polymorphism) and TPH2 (G703T polymorphism), and serotonin receptors (HTR2C and HTR2A genes). The association of the regulatory and adaptive status of a subject with the polymorphism of serotonergic mediator system genes was revealed.

Detection of flashing areas attributed to the frog cardiac function in the vagosympathetic trunk placed into a high frequency electric field.

In a high frequency electric field, two flashing areas were observed during each contraction of the heart in the vagosympathetic trunk of a paralyzed frog with an intact brain. One area with a higher diameter was moving along the nerve from the heart at a speed of 16.6 ± 0.2 m/s. It was identified as afferent. Another area with a smaller diameter was spreading along the nerve towards the venous sinus of the frog heart at a speed of 5.6 ± 0.3 m/s, and it was efferent.

[The influence of level of arterial pressure on regulatory-adaptive status].

People with increased arterial pressure have more low regulatory-adaptive abilities than people with normal arterial pressure. The achievement of target blood pressure level with antihypertensive drugs is accompanied by normalization the regulatory-adaptive abilities. It is true only for people who had arterial hypertension less than 160/90 mm Hg until treatment.

[Quantitative characteristic of the regulatory and adaptive status for the estimation of severity of chronic cardiac failure].

A method for the estimation of severity of chronic cardiac failure (CCF) based on the quantitative evaluation of the regulatory and adaptive status (RAS) of the organism. Patients with FC I-III HCF concomitant with grade I-III hypertensive disease and/or coronary heart disease underwent cardiorespiratory synchronism test for the quantitative estimation of RAS (6 min walk), echocardiography, treadmill measuring maximum oxygen consumption (VO2max), measurement of plasma N-terminal precursor of brain natriuretic peptide. The lowering of RAS was especially pronounced when HCF FC changed from I to III, in agreement with results of traditional instrumental and laboratory tests. Specifically, left ventricle systolic and diastolic function was impaired, tolerance of physical exercise decreased while neurohumoral regulation was activated. There was positive correlation between RAS indices at HCF CF I and II for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for N-terminal precursor of brain natriuretic hormone. At HCF FC II and III, positive correlation was documented for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for the N-terminal precursor of brain natriuretic hormone. It means that the qualitative estimate of RAS obtained in the cardiorespiratory synchronism test can be used to assess severity of HCF in patients with hypertensive disease and/or coronary heart disease.

[Advantages of quinapril therapy in patients with arterial hypertension and functional class III chronic heart failure with preserved left ventricular ejection fraction].

AIM: To determine advantages of therapy of functional class (FC) I-II chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction in patients with hypertensive disease (HD) with metoprolol succinate or quinapril and to assess their effect on regulatory-adaptive status. METHODS: Two hundred patients with I-II FC CHF and LVEF >50% at the background of stage I-II hypertensive disease participated in this study. They were randomized into 2 groups. Group I comprised 104 patients (mean age 52.8+1.9 years) who were prescribed metoprolol succinate 87.7+/-7.6 mg/day. Patients of group 2 (n=96, mean age 55.0+/-1.4 years) were prescribed quinapril 21.0+55 mg/day. Examination at baseline and after 6 months of therapy included 6 min walk test, treadmillometry with assessment of maximal oxygen consumptiion (VO2max), echocardiography, 24 hour blood pressure monitoring, measurement of N-terminal precursor of brain natriuretic peptide (NT-proBNP); test of cardio-respiratory synchronism was used for objective qualitative determination of the state of the ,renin-angiotensin system. RESULTS: Both drugs improved parameters of LV diastolic function, but only quinapril effectively changed LV structural geometric parameters and systolic function. Only treatment with quinapril was associated with improvement of RAS, elevation of tolerance to physical effort, and increased VO2max. Quinapril more substantially lowered level of NT-proBNP. CONCLUSION: Quinapril has an advantage over metoprolol succinate in therapy of patients with FC I-II CHF and preserved LF EF at the background of stage I-II HD.

[The regulatory-adaptive status in the evaluation of human stress-resistance].

There was offered a method of human stress-resistance evaluation via the dynamics of the regulatory-adaptive status. The regulatory-adaptive status was being determined via the parameters of the cardiorespiratory synchronism in the original state and at the application of the stress factor. Individuals, whose regulatory-adaptive status didn't change or decreased by not more than 5-6% at the exposition to the stress factor formed the group with a high level of stress-resistance. The individuals, whose regulatory adaptive status at the exposition to the stress factor decreased by less than 50% formed a group with a moderate level of stress-resistance. The examinees, whose regulatory-adaptive status decreased by more than 50% in a response to the stress factor were set in a group with a low stress-resistance level. The method was tested in the three stress models: 1) exam stress-on 58 students; 2) parachute jump stress-on 35 beginner parachutists; 3) stress, caused by the relocation to the zone of the catastrophe on 30 rescuers. In all the three models the method is highly informative. At the same time the levels of the stress-resistance were being evaluated by the psychological methods. It was shown, that the evaluation of the stress-resistance level via the dynamics of the regulatory-adaptive status allows to objectively characterize the ability of an individual to resist stress and should be included in the test complex for the casting of the candidates for the extreme professions.

[Alternative therapy with ivabradine in patients with functional class III chronic heart failure].

Aim of the study - to determine efficacy of therapy with the use of ivabradine in patients with functional class (FC) III chronic heart failure (CHF) on the basis of assessment of its action on regulatory adaptive status (RAS). We included into the study 100 patients with FC III CHF at the background of ischemic heart disease (IHD) and/or stage III hypertensive disease (HD) receiving complex therapy (quinapril, torasemide, spironolactone). After randomization group 1 comprised 56 patients (age 62.9+/-1.8 years) who were prescribed slow release metoprolol succinate (59.1+/-4.5 mg/day). Group 2 comprised 44 patients (age 59.4+/-1.3 years) who were prescribed If channel inhibitor ivabradine (12.1+/-2.3 mg/day) if beta-blocker use was not possible. Examination at baseline and in 6 months included treadmillometry with assessment of maximal oxygen consumption (VO2 max) at exercise, echocardiography, 24-hour blood pressure monitoring, measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood plasma. For objective qualitative assessment of the state of RAS we used a test of cardio-respiratory synchronism. Therapy with the use of ivabradine improved structural and functional state of the myocardium, elevated tolerance to exercise, caused positive changes of NT-proBNP concentration in blood plasma and VO2 max at exercise. Thus ivabradine probably can serve as alternative to -adrenoblockers when their use is not possible patients with FC III CHF at the background of IHD and/or stage III HD.

Assessment of therapeutic drug efficiency.

The efficiency of drug therapy should be evaluated by not only its directed action on specific organ or target parameter, but also its effects on general regulatory and adaptive status.

[Cardiorespiratory synchronism: revealing in human, dependence on properties of nervous system and functional states of an organism]. / Serdechno-dykhatel'nyi sinkhronizm: vyiavlenie u cheloveka, zavisimost' ot svoistv nervnoi systemy i funktsional'nykh sostoianii organizma.

Cardiorespiratory synchronism (CRS) shows that at the breathing frequency, which as usual exceeds the baseline heart rhythm, the heart makes one contraction per each breathing. It is shown that CRS arises as a result of reproduction by the heart the rhythm of signals, coming to the heart via vagus nerves. CRS characterized by the synchronization range, duration of its development after the beginning of the rapid respiration, difference between the baseline heartbeat frequency and lower limit of synchronization range. The CRS parameters were determined in humans at the age of 5-65. The CRS parameters depends on nervous system type, vegetative tonus of the nervous system and functional states of an organism.

New diagnostic potentialities of cardiorespiratory synchronization in children.

The study demonstrated that the method of cardiorespiratory synchronization provides valuable information on the nature of arrhythmia and helps to evaluate the regulatory adaptive potentialities of a child. The width of synchronization range and the latency of synchronization at the lower boundary are the indicators of regulatory adaptive potentialities.

Cardiorespiratory synchronism in the evaluation of adaptive reaction in children.

Parameters of cardiorespiratory synchronism were studied in children under conditions of psychoemotional stress. The results indicate that the upper limit of the cardiorespiratory synchronism, synchronization range, and the difference between the upper limit and the initial heart rate are the parameters of synchronism, which allow estimation of the normal adaptive reaction and thus help to evaluate health status in children.

[Protective electrophysiological effects of somatostatin in patients with paroxysmal atrioventricular reciprocal tachycardias]. / Kupiruiushchee deistvie i élektrofiziologicheskie éffekty somatostatina u bol'nykh s paroksizmal'nymi atrioventrikuliarnymi retsiproknymi takhikardiiami.

Within 30 seconds after intravenous injection of somatostatin (sandostatin, 0.1 mg) we observed restoration of sinus rhythm in patients with atrioventricular (AV) junctional or orthodromic reciprocal tachycardias. This action was associated with interruption of re-entry on anterograde direction of AV conductivity. Somatostatin elicited pronounced cardiac electrophysiological effects which were due to activation of parasympathetic nervous system. Besides, it evoked transient elevation of systolic (+12.6%) and diastolic (+13.5%) blood pressures. High efficacy and good tolerance of somatostatin allow to consider this peptide as an alternative to adenosine and verapamil in the treatment of AV reciprocal tachycardias.

[Effect of regulatory peptides on the effect of cardiorespiratory synchronization in patients with heart diseases]. / Deistvie reguliatornykh peptidov na éffekt kardiorespiratornyi sinkhronizatsii u bol'nykh s patologiei serdtsa.

A long-acting somatostatin analogue (sandostatin) and synthetic opioid dalargin were examined for the effect on the heart rhythm under the cardiorespiratory synchronization test in patients with heart disease. In high-frequency respiration synchronized with photostimulator flashes the patients exhibited cardiorespiratory synchronism when heart rate corresponds exactly to respiration rate. A spontaneous change of the respiration rate entailed corresponding changes in the heart rate. This allowed regulation of the heart rhythm. Intravenous injection of sandostatin or dalargin extended the range of the cardiorespiratory synchronization. The latter points to involvement of peptides in mechanisms of heart taking of the control signals coming from the central nervous system.

Cardiotropic effects of Met-enkephalin and somatostatin under conditions of neurotensin receptor blockade.

Pretreatment with the neurotensin receptor antagonist decreased the severity and time of Met-enkephalin-induced inhibition of vagal chronotropic effects in cats. The opiate receptor antagonist naloxone produced a delayed inhibitory effect on the synchronizing component of the vagal chronotropic effect under conditions of neurotensin receptor blockade. Cardiotropic effects of somatostatin remained unchanged during neurotensin receptor blockade. These data indicate one-way and two-way interactions between peptides modulating parasympathetic cardiac regulation.

[The regulatory effects of opioid peptides--enkephalins--in controlling the activities of the cardiovascular system]. / Reguliatornye éffekty opioidnykh peptidov--énkefalinov v kontrole deiatel'nosti serdechno-sosudistoi sistemy.

In this review we analyse the experimental and clinical findings demonstrating important regulatory significance of met-enkephalin, leu-enkephalin and their derivatives in the control of cardiovascular system activity. Enkephalin-positive immunoreactivity is revealed in the heart of different species of animals, and their cardiovascular effects are established in numerous investigations. It is determined that cardiac effects of enkephalins are essentially associated with modulatory influence at the presynaptic and postsynaptic levels on the activity of extracardiac neural regulation. Cardiovascular effects of endogenous opioid system are extremely important in developing of myocardial ischemia, cardiac arrhythmias and congestive heart failure. The cellular mechanisms of opioid effects are associated with stimulation of mu- and delta-subtypes of opiate receptors which stimulation of mu- and delta-subtypes of opiate receptors which are coupled with conductivity of ion channels, adenylate cyclase activity, phosphoinositide turnover and calcium-calmodulin-dependent protein kynases.

[The dynamics of the chronotropic effect of a single vagal stimulus in cats under the action of met-enkephalin and neurotensin]. / Dinamika khronotropnogo éffekta odinochnogo vagusnogo stimula u koshek pri deistvii met-énkefalina i neirotenzina.

Following a burst of pulses applied to the vagus nerve with progressively incremental delay after the P wave of the ECG, the narrow zone of the cardiac cycle was identified where even a small shift of the vagal burst position evoked an abrupt alteration of the chronotropic effect magnitude. Met-enkephalin potentiated the phase-dependent vagal chronotropic effect, whereas neurotensin moved its limits toward the initial part of the P-P interval.