[EFFECTIVENESS OF FIXED COMBINATION OF PERINDOPRILARGININE AND AMLODIPINE FOR THE TREATMENT OF ARTERIAL HYPERTENSION WITH CONCOMITANT CHRONIC CARDIAC INSUFFICIENCY AND SIGNS OF CHRONIC KIDNEY DISEASE].

AIM: to study effectiveness of a fixed combination of perindopril arginine and amlodipine besylate for the treatment of arterial hypertension with concomitant chronic cardiac insufficiency and signs of chronic kidney disease Materials and methods: 53 (44.9%) patients aged 64.5±8.2 yr with signs of chronic kidney disease (CKD) were selected from 118 subjects with grade II-III essential AH and chronic cardiac insufficiency They had an increased blood cystatin C level (mean 1.4±0.3 mg/l) and/or decreased glomerular filtration rate (GFR) calculated by 3 formulas: 77.6±15.9 (MDRD), 79.3±17.1 (CKD-EPI) and 57.7±15.2 ml/min/1. 73 m3 (from cystatin C level). Fixed combinations of perindopril arginine and amlodipine besylate (5/5, 5/10, 10/10 mg) were used to treat the patients. Their effectiveness was evaluated 2 months after the onset of therapy based on results of AP measurement, 24 hr AP monitoring, assessment of clinical conditions and 6 min walk test. Blood creatinine, urea and cystatin C levels and GFR were measured. RESULTS: Target AP was achieved in 82.6% of the patients. Systolic AP (SAP) decreased significantly from 172±11.2 to 135.7±8.2 mmHg (p<0.01), diastolic AP (DAP)from 110±6.9 to 85.3±7.2 mm Hg (p<0.5). Mean daily SAP and DAP decreased by 14.7 and 14.4% respectively. SAP and DAP load also decreased Clinical conditions estimated in terms of the CCI functional class improved (a decrease from 6.2±1.1 to 4.2±1.3 scores (p<0.01)). Tolerance of physical activity increased from 157.2±12.6 to 320.4±32.2 m (p<0.05). Blood cystatin C level decreased and GFR increased. CONCLUSION: The fixed combination of perindopril arginine and amlodipine besylate ensures high therapeutic effect in patients with arterial hypertension and concomitant chronic cardiac insufficiency having signs of chronic kidney disease.

α-conotoxins revealed different roles of nicotinic cholinergic receptor subtypes in oncogenesis of Ehrlich tumor and in the associated inflammation.

Multiple injections of conotoxin MII, a blocker of alfa3-ß2 and alfa6-containing subtypes of nicotinic acetylcholine receptors (n-AChRs), as well as conotoxin ArIB11L16D, a blocker of alfa7 subtype n-AChR, at a dose of 1 nmol/kg reduce both the lactate dehydrogenase level in tumor cells and the inflammatory leukocyte infiltration in tumor tissue in mice bearing Ehrlich carcinoma. The first stage of pathomorphism was detected in the tumor tissue after the treatment with the ArIB11L16D conotoxin, whereas the second stage was observed after the treatment with conotoxins RgIA and MII. Only MII injections led to a significant reduction in tumor growth. Our results show the involvement of n-AChRs in the regulation of metabolic processes and cell-cell interactions related to carcinogenesis and tumor-associated inflammation.

[Evidences of Existence of Serotoninergic Nerves, Enhancing Duodenal Motility].

The review is devoted to the mechanism of duodenal motility activation caused by sympathetic nerves. The authors havefound that stimulation of the sympathetic trunk in the thoracic cavity in dogs in most cases provide not inhibitory but excitatory motor responses of the duodenum. Excitatory effects were eliminated during 5HT-receptors blockade by promedol and lysergol. Analysis ofpublications showed that sympathetic trunk contains serotoninergic fibers, providing excitatory motor responses of the duodenum to electrical nerve stimulation. According to histochemical and physiological studies, amount of serotonergic fibers in the sympathetic trunk is several times more than the adrenergic. This means that the body has sertoninergic nerves. Serotoninergic nerve as well as the sympathetic is a collective notion. There are: sympathetic trunks, their ramifications and branches that innervate the internal organs. Since promedol blocks serotonergic nerves, this is plausible cause of constipation in patients after surgical treatment along with the application of this drug.

[Therapy of Arterial Hypertension in Patients With Chronic Heart Failure and Signs of Chronic Kidney Disease With Fixed Perindopril/Amlodipine Combination].

PURPOSE: to assess efficacy of a fixed combination of perindopril arginine and amlodipine besylate in the treatment of hypertensive patients with chronic heart failure (CHF) and signs of chronic kidney disease (CKD). MATERIAL AND METHODS: Persons with CKD (n=53, age 64.5+/-8.2years) were selected from 118 patients with grade 2-3 essential hypertension with CHF. Presence of CKD was confirmed by elevated blood levels of cystatin C and lowered glomerular filtration rate (GFR). Used doses of fixed perindopril/amlodipine combination were 5/5, 5/10, 10/10mg. Efficacy was assessed after 2 months of therapy on the basis of results of the examination which included clinical blood pressure (BP).

[The ultrastructural organization of the liver of rats with experimental hepatitis after drinking mineral water containing humic acids].

We undertook the ultrastructural analysis of liver parenchyma taken from male rats with experimental hepatitis induced by the administration of paracetamol at a dose of 1000 mg per 1 kg body weight either following a course of drinking mineral water containing humic acids at a concentration of 20 mg/sq. decimeter) or 14 days after the termination of the drug action (the after-effect phase). It was shown that the consumption of mineral water during 21 days resulted in the modification of the ultrastructural organization of hepatocytes apparent as the increased amount of cisterns in the granulosa endoplasmic system, glycogen rosettes, and mitochondrial polymorphism. These changes give evidence of the restoration of the energy, glycogen and protein synthesizing functions disturbed by paracetamol administration. The after-effect phase was characterized by the further strengthening of reparative processes and the functional activity of hepatic cells.

Effect of adrenoblockers on slow (LF) waves in rabbit heart rate.

Propranolol and atenolol were used to examine the role of the adrenergic system in the genesis of slow HR variations (waves) in rabbits, the animals characterized by pronounced sympathetic influences. The control experiments were performed with physiological solution and long-term records in intact rabbits. The harmonic (spectrum) analysis was performed with fast Fourier transform. The adrenoblockers produced no decrease in the power of slow waves. The study did not found the sympathetic genesis of slow variations in rabbit HR.

[Vegetative regulation of the cardiovascular system in patients with chronic heart failure with chronic renal insufficiency].

This review deals with vegetative regulation of cardiovascular system in patients with chronic heart failure (CHF) and signs of chronic renal insufficiency. CHF is currently regarded as a disturbance of neurohumoral mechanisms controlling blood circulation. At the same time, both prognosis and outcome of CHF depend on the presence of chronic renal insufficiency whose pathogenesis is poorly understood The authors emphasize the importance of elucidation of common pathogenetic mechanisms of these mutually complicating conditions.

Chronotropic and inotropic components of cardiac reflexes in cats.

The relationship between chronotropic and inotropic components of cardiac reflexes were studied in cats using intravenous blood injections, occlusion of the abdominal aorta, pressing on eyeballs (Aschner maneuver), and occlusion of the carotid arteries. Inotropic reactions were characterized by the contractility index DPxHR/MSAP. Different reflexes were shown to be characterized by different ratio of chronotropic and inotropic components, in addition, heart rate and contractility were often altered in opposite directions.

Chronotropic and dromotropic components of cardiac reflexes in the cat.

The relationship between dromotropic and chronotropic components of various cardiac reflexes was studied in cats. Intravenous infusion of blood was mainly accompanied by unidirectional negative chronotropic and dromotropic effects, but the dynamics of these effects was different. Clumping of the carotid arteries in most animals induced unidirectional negative chronotropic and dromotropic effects. Their dynamics was also different and differed from that observed during intravenous blood infusion. Pulsatile increase in blood pressure in the carotid artery was accompanied by a unidirectional negative effect in the majority of animals. The opposite chronotropic and dromotropic effects with similar temporal dynamics were revealed in 1/3 animals. The ratio of positive and negative effects was similar during clumping of the abdominal aorta (1/3 unidirectional, 1/3 opposite, and 1/3 isolated chronotropic and dromotropic effects). Aschner test was characterized by the prevalence of isolated chronotropic effect (negative effect in the majority of animals; positive effect in 1/3 animals). Hence, different cardiac reflexes are characterized by different ratio between chronotropic and dromotropic components.

Effect of pentobarbital on spectral characteristics and phase ratios of wave oscillations of cardiac contraction period and time of atrioventricular conduction in cats.

Effects of pentobarbital on spectral characteristics and phase ratios of wave oscillations of the cardiac contraction period (RR interval) and time of atrioventricular conduction (AV interval) were studied in experiments of cats. Pentobarbital moderately reduced the mean values of both intervals and significantly reduced their standard deviations and spectral powers in all frequency bands (high-frequency, low-frequency, and very low-frequency). Pentobarbital treatment led to deceleration of breathing, the frequency range of respiratory oscillations of RR and AV intervals shifted in some cases from high to low frequencies; evaluation of spectral power in the intermittent band corresponding to respiration frequency (instead of standard fixed high-frequency band) showed that pentobarbital suppressed the respiratory oscillations in these bands. Pentobarbital induced inversion of phase ratio between respiratory oscillations of RR and AV intervals: oscillations of both intervals before pentobarbital coincided by phase, while after pentobarbital injection they were in antiphase. The mechanisms of the latter phenomenon deserve further investigation.

Role of sympathetic and parasympathetic nervous systems in heart rate regulation in cats.

The effects of atropine and beta-adrenoceptor blockers on mean HR, wave structure of the cardiac rhythm, and chronotropic reaction to noise stress were examined in cats. Atropine (0.5 mg/kg) increased the mean HR and significantly decreased the spectrum power of HF, LF, and VLF oscillations. The decrease in HF power was most pronounced, which enhanced LF/HF ratio. Propranolol (0.5 mg/kg) decreased the mean HR and slightly increased the power of HF, LF, and VLF oscillations. Atenolol (2 mg/kg) exerted similar but more pronounced effects. beta-Adrenoceptor blockers increased HF power to a greater extent than LF and VLF power, which led to a decrease in LF/HF ratio. Atropine markedly decreased the chronotropic reaction to stress. beta-Adrenoceptor blockers produced no effect on the amplitude of this reaction, but accelerated restoration of initial HR. It is established that the changes in power spectrum of HR and the phase reflex reactions in cats are mediated by parasympathetic influences; the sympathetic system is involved only in the control of mean HR, probably in response to the level of animal activity. The changes in LF/HF ratio during blockade of sympathetic and parasympathetic systems are caused by opposite influences of these systems on HF oscillations, but not by hypothetic "sympathetic" and "parasympathetic" nature of LF and HF oscillations of the heart rhythm.

Frequency parameters of feline left ventricular pressure under various experimental conditions.

Cardiac frequency-domain parameters of the left ventricular pressure were studied in acute experiments on cats under conditions of reflex and load stimulation and during maximum inotropic stimulation with epinephrine. A strict correlation was revealed between the upper threshold of the frequency range and the maximum value of pressure first derivative. Without epinephrine infusion, the maximum value of pressure first derivative and the upper threshold of the frequency range attained 9840 mm Hg/sec and 98.4 Hz, correspondingly. During epinephrine infusion, the corresponding values were 12911 mm Hg/sec and 145 Hz. Left ventricular pressure in cats is characterized by high-frequency parameters, which can be measured by special catheter microtransducers and only in some cases by routine pressure gauges.

Whether independent regulation of myocardial contractility and diastolic relaxation rate is possible?

In acute experiments on cats neural inotropic and lusitropic reactions of the heart to enhancement of pre- and afterload were assessed by changes in contractility and relaxation indices, which were preliminary chosen for their maximum specificity and sensitivity. The control cardiac responses to increased pre- and afterload were measured after treatment with ganglionic blocker arfonad. The myogenic component of these responses assessed under the action of arfonad was highly pronounced, therefore the neural inotropic and lusitropic reactions were measured as the difference between load-induced changes of indices in experiments with and without arfonad. Increased preload produced similar negative inotropic and lusitropic effects, while increased afterload produced a more pronounced negative inotropic effect, which indicated independent regulation of contractility and diastolic relaxation of the heart.

Comparison of different cardiac relaxation indices.

Sensitivity (response to epinephrine infusion) and specificity (response to changes in pre- and afterload) of some cardiac relaxation indices were compared in acute experiments on cats treated with ganglionic blocker arfonad. Some new indices proposed by us provide better characteristics than widely used relaxation time constant (t) and maximum first derivative of the left ventricular pressure (-dP/dt)max.

Contraction and relaxation indices in the study of neural inotropic and loositropic influences on the heart.

The possibility of using contraction and relaxation indices for evaluation of inotropic and loositropic influences on the heart was studied in experiments on cats. Increased pre- and afterload were used as the stimuli, which are simultaneously loading and reflexogenic. Under conditions of preserved innervation both stimuli elevated the indices selected according to the highest sensitivity/specificity ratio. Ganglionic blocker arfonad potentiated the effects of these stimuli. This attests to a considerable contribution of the myogenic component to the changes in the studied indices in response to increased pre- and afterload and to the existence of negative inotropic and loositropic influences on the heart under conditions of preserved innervation. These conclusions were supported when more specific indices were used: in most cases they decreased during load tests. Thus, when the contraction and relaxation indices are used for evaluation inotropic and loositropic influences on the heart, it seems reasonable either to compare heart responses under conditions of preserved or blocked innervation, or to apply more specific indices. Analysis of changes in most widely used indices (dP/dt)max and t showed that t reliably reflects neural loositropic influences, while the use of (dP/dt)max without proper control can be erroneous.

[Morphofunctional characteristics of the ovaries, thyroid gland and adrenal glands in experimental lead acetate poisoning]. / Morfofunktsional'naia kharakteristika iaichnikov, shchitovidnoi zhelezy i nadpochechnikov pri éksperimental'nom otravlenii uksusnokislym svintsom.

Daily doses of 50 mg/kg of lead acetate injected into the laboratory animals induce morphologic changes in the parenchyma of ovaries, thyroid gland, adrenals and compromises neural mediating processes in paraventricular and supraoptic nuclei of hypothalamus. The observed morphologic changes are similar to those characteristic for intensive functioning. Prolonged exposure to lead acetate (daily dose 10 mg/kg) results in adaptation and compensation, which preserves the functional potential of the organs. The morphologic changes in the endocrine organs do not lead to significant hormonal changes.

[Neural regulatory effects on the contractility of heart ventricles]. / Izuchenie nervnykh reguliatornykh vliianii na sokratimost' zheludochkov serdtsa.

As a result of acute experiments on cats we revealed the approaches to choosing the best indices of the contractility of the left and the right cardiac ventricles in the concrete conditions of the experiment on the basis of the original criterion of optimality. For revealing neural inotropy influences we suggest the index based on the combined changes of optimum indices. A new approach to revealing reflex influences on contractility in the conditions of intact blood circulation is worked out, which is based on the comparison of these influences with the control changes of haemodynamic parameters.

[Myocardial contractile indices as a means for studying the inotropic reactions of the different heart chambers in a computerized experiment]. / Indeksy sokratimosti miokarda kak sredstvo izucheniia inotropnykh reaktsii razlichnykh kamer serdtsa v komp'iuternom éksperimente.

Artifacts which can distort the heart chambers contractility indices and the ways of its prevention are discussed. Changes in the heart pre- and afterload causing an inotropic effects, are analysed. Recommendations on the computer systems for recording and processing of blood pressure parameters in physiological experiment, are given.