[Features of autonomic regulation of the cardiovascular system in human late ontogenesis.]

Using the method of arterial piezopulsometry, statistical and spectral analyzes of variable parameters (VmaxPP and TNN) of pulse waves of blood pressure in patients aged 18 to 85 years were performed. The individual characteristics of the autonomous (vegetative and neuroendocrine) regulation of the muscular effectors (ME) of the cardiovascular system (CVS) in an elderly man (75 years old) and a young woman (20 years old) were estimated with high accuracy. These data, as well as the results of a comparative study of patients of different ages, made it possible to identify a certain pattern of directed change in the sympathoadrenal regulation of ME CVS in human ontogenesis. It is concluded that in the course of their lives, people undergo a restructuring of the physiological mechanism of the autonomous regulation of their ME CVS, aimed at replacing short-term sympathetic regulation in young people with more effective and more stable regulation by humoral catecholamines in elderly.

Effects of Pinacidil and Calcium on Succinate-Energized Rat Heart Mitochondria in the Presence of Rotenone.

The effect of pinacidil was studied on calcium-loaded rat heart mitochondria (RHM) in the presence of succinate and rotenone. In experiments with pinacidil, the swelling of these mitochondria increased in media with NH4NO3 or K-acetate, but the inner membrane potential (ΔΨmito) and the respiration in 3 or 2,4-dinitrophenol-stimulated states of these organelles decreased due to the opening of the mitochondrial permeability transition pore (MPTP) in their inner membrane. These effects were inhibited by cyclosporin A and ADP. It was concluded that the protective effect of pinacidil in the cardiac muscle under ischemia/reperfusion may be associated with both the stimulation of mitochondrial swelling and a decrease in RHM calcium overload resulted in ΔΨmito fall due to mild uncoupling effect of pinacidil.

[AGED CARDIOHEMODYNAMICS COMPLICATED BY STROKE].

A new method of arterial piezopulsometry allowed a 12-year study of the peculiarities of age-related changes in cardiac hemodynamic indices in an aged man after ischemic stroke. The ob-tained results enable use of these indicators as prognostic criteria of an individual organism's re-sistance to acceleration factors of aging, as well as its resistance to the development of the cardi-ovascular pathology caused by the stroke. Simultaneous dual registration of piezopulsograms al-lowed establishing a significant increase of the augmentation index of pulse pressure (AIxPP) and the velocity of the pulse wave of blood pressure propagation through the radial artery (Var) in a paralyzed right arm, compared to the left hand control (p < 0,05). Range fluctuations in the relative values of this difference can serve as an objective indicator of the functional state of a paralyzed arm of a patient during rehabilitation treatment, and a sharp decrease of this difference and its subsequent stabilization can serve as an indicator of the beginning of recovery.

[COMPARATIVE STUDY OF Y³âº EFFECT ON CALCIUM-DEPENDENT PROCESSES IN FROG CARDIAC MUSCLE AND IN MITOCHONDRIA OF RAT CARDIOMYOCYTES].

Inotropic effects of yttrium acetate (Y³âº) on contractions of myocardium preparations of the frog Ra- na ridibunda as well as on respiration and the inner membrane potential (Δψmito) of isolated rat heart mi- tochondria were studied. It was found that 2 mM yttrium in Ringer solution significantly reduced the am- plitude of myocardium contractions evoked by electric stimulation and increased the half-relaxation time (n = 5). In experiments with Ca²âº, Y³âº decreased Ca²âº-dependent oxygen consumption rate of rat heart mitochondria, energized by glutamate and malate, impeded the reduction in respiration of these mito- chondria in state 3 or uncoupled by 2,4-dinitrophenol, and inhibited Ca²âº-induced decrease in their inner membrane potential. These data are important to better understand the mechanisms of Y³âº effects on myocardial calcium-dependent processes. Possible mechanisms of negative inotropic effect of Y³âº on the myocardium and its influence on the Ca²âº-dependent processes in rat mitochondria are discussed.

[MECHANISMS OF THE EFFECT OF Li+ ON MYOCARDIUM OF VERTEBRATES].

The effect of Li+ on the frog Rana temporaria myocardium and its influence on the ion transport in the rat heart mitochondria (RHM) were studied. Li+ added to the normal Ringer solution (Li(+)-R) was found to attenuate myocardial tension, decrease the maximal rate of tension development and its half-relaxation time. Comparison of the cardiac muscle contraction parameters in the Li(+)-R with the effect of the voltage-gated Ca(2+)-channels (Cav1.2), verapamil and CdCl2, showed that the negative inotropic effect of the Na+ replacement by Li+ in the limited intermembrane ("fuzzy") space is underlain by the blocking of Ca2+ influx into the myoplasm via the reverse Ca2+/Na(+)-exchanger in the plasma membrane (PM). This, in turn, prevents Ca(2+)-induced massive Ca2+ release into the myoplasm via the RYR2-channels in the sarcoplasmic reticulum (SR) leading in aggregate to suppression of Ca(2+)-dependent myocardial contractions. In the experimental studies of the Li+ effect on the RHM it was established that Li+ just slightly increases the passive permeability of the inner mitochondrial membrane (IMM) for K+ and H+ and decreases the intensity of ion pumping out of the energized mitochondrial matrix to the external medium. This may also indicate the lack of relationship between the mitochondrial oxidative processes and the reduction in the myocardial contractile activity under the Na+ replacement by Li+.

[Action of yttrium on calcium-dependent processes in myocardium of vertebrates].

This work deals with study, of effect of yttrium acetate (Y3+) on myocardium of the frog Rana redibunda and of its action on the ion transport across the inner membrane of the rat heart mitochondria. It was found that Y3+ decreased strength of heart contractions and facilitated transport of ions in rat heart mitochondria stimulated by 10 mM glutamate and 2 mM malate. In the presence of Y3+, the energy-dependent transport of Ca2+ in mitochondria was inhibited; this was manifested as a decrease of their swelling in the medium containing 125 mM NH4NO3 and Ca2+ or 25 mM potassium acetate, 100 mM sucrose and Ca2+. It is assumed that the Y(3+)-caused decrease of the heart muscle contractility is not only due to its direct blocking effect on the potential-operated Ca2+ channels of the pacemaker and contractile cardiomyocytes, but also due to its mediated action on active transport of Ca2+ in mitochondria. The data that Y3+ activates transport of K+ via the mitochondrial potassium uniporter and blocks Ca(2+)-channels of the inner mitochondrial membrane are important for better understanding of mechanisms of action Y3+ on cardiomyocytes of vertebrate animals and humans and the possible use of Y3+ in medicine.

[Inotropic effect of a new probiotic product on myocardial contractility. Comparison with diazoxide].

The inotropic effect of a new probiotic product on myocardial contractility of the frog Rana ridibunda and the effect of probiotic product on the rat cardiac mitochondria swelling were studied. In both cases, the comparison with known cardioprotector diazoxide was done. Probiotic product and diazoxide were shown to cause a dual effect on the maximum force induced by the muscle sample during spontaneous atrial contraction. Addition of agents caused a negative impact, while washing out exerted a positive inotropic effect. At the same time probiotic product has virtually no effect on the amplitude of contraction induced by electrical stimulation of the ventricle fragments. Probiotic product decreases both proton passive permeability in the inner mitochondrial membrane, and potassium active transport in mitochondria caused by activation of K(+)-uniporter of cardiomyocytes. A possible mechanism of action of probiotic product is discussed.

[Action of La3+ on the systems providing contractility of vertebrate myocardium].

The inotropic action of La3+ on frog myocardium was studied with taking into account of its effect on mitochondria of cardiomyocytes (CM). It has been established that in the range of studied concentrations (0.2-6 mM), La3+ decreases dose-dependently the strength of cardiac contractions (by 3.3-92.2 %). In parallel experiments on isolated rat heart mitochondria (RHM), La3+ at a concentration of 25 microM has been shown to cause swelling of non-energized and energized mitochondria in isotonic medium with 125 mM NH4NO3 and in hypotonic medium with 25 mM CH3COOK. The study of oxidative processes in mitochondria with aid of polarographic method of measurement of oxygen concentration has shown that La3+ at concentrations of 50 and 100 microM increases the oxygen consumption rate by mitochondria in the state 2. However, La3+ does not decrease the respiration rate of isolated mitochondria in the state 3, as this takes place in the case of use of Cd2+ or at the Ca(2+)-overloading of mitochondria. The rate of endogenous respiration of isolated mitochondria in the medium with La3+ was higher than in control, which implies its effect on ion permeability of the inner membrane. The data obtained in this work indicate that the La(3+)-produced decrease of the contractility of cardiac muscle is not only due to the direct blocking effect on the potential-controlled Ca2+ channels, but is also mediated by its unspecific action on the CM mitochondria. This action is manifested in acceleration of the energy-dependent K+ transport in matrix and in an increase of ion permeability of the inner mitochondrial membrane (IMM).

[Influence of oxidative processes in mitochondria on contractility of the frog Rana temporaria heart muscle. Effects of cadmium].

The inotropic Cd2+ action on frog heart is studied with taking into account its toxic effects upon mitochondria. Cd2+ at concentrations of 1, 10, and 20 microM is established to decrease dosedependently (21.3, 50.3, and 72.0%, respectively) the muscle contraction amplitude; this is explained by its competitive action on the potential-controlled Ca2(+)-channels of the L-type (Ca 1.2). In parallel experiments on isolated rat heart mitochondria (RHM) it was shown that Cd2+ at concentrations of 15 and 25 microM produces swelling of non-energized and energized mitochondria in isotonic (with KNO2 and NH4NO3) and hypoosmotic (with 25 mM CH3COOK) media. Study of oxidative processes in RHM by polarographic method has shown 20 microM Cd2+ to disturb activity of respiratory mitochondrial chain. The rate of endogenous respiration of isolated mitochondria in the medium with Cd2+ in the presence of malate and succinate was approximately 5 times lower than in control. In experimental preparations, addition into the medium of DNP-uncoupler of oxidation and phosphorylation did not cause an increase of the oxygen consumption rate. Thus, the obtained data indicate that a decrease in the cardiac muscle contractility caused by Cd2+ is due not only to its direct blocking action on Ca2(+)-channels, but also is mediated by toxic effect on rat heart mitochondria, which was manifested as an increase in ion permeability of the inner mitochondrial membrane (IMM), acceleration of the energy-dependent K+ transport into the matrix of mitochondria, and inhibition of their respiratory chain.

[Influence of mitochondrial oxidative reactions on myocardial contractility. Effects of Ni2+].

Inotropic effects of Ni2+ and mitochondrial oxidative readions were accordingly tested by the use of frog myocardial preparations, excised from left frog ventricle, and rat heart mitochondria (RHM). Amplitude of the cardiac contraction was increased in the presence of 10-200 microM Ni2+ in dose-dependent manner. It was found that Ni2+ is not toxic for RHM. State 4 in a KCI medium was stimulated by 100 microM Ni2+. At the same time, Ni2+ did not affected state 3 and 2,4-dinitrophenol-stimulated respiration of RHM. Our findings allow to be supposed that Ni2+-induced increase in the amplitude of the cardiac contraction can be affected by energetic state of RHM.

Features of mitochondrial energetics in living unicellular eukaryote Tetrahymena pyriformis. A model for study of mammalian intracellular adaptation.

Tetrahymena pyriformis is used in diverse studies as a non-mammalian alternative due to their resemblance in many main metabolic cycles. However, such basic features of mitochondrial energetics as Delta psi (electrical potential difference across the inner mitochondrial membrane) or maximal stimulation of respiration by uncouplers with different mechanisms of uncoupling, such as DNP (2,4-dinitrophenol) and FCCP (p-trifluoromethoxycarbonylcyanide phenylhydrazone), have not been studied in living ciliates. Tetrahymena pyriformis GL cells during stationary growth phase after incubation under selected conditions were used in this study. Maximal stimulation of cellular respiration by FCCP was about six-fold, thus the proton motive force was high. The DNP uncoupling effect was significantly lower. This suggests low activity of the ATP/ADP-antiporter, which performs not only exchange of intramitochondrial ATP to extramitochondrial ADP, but also helps in the uncoupling process. It participates by a similar mechanism in electrophoretic transport from matrix to cytosol of ATP(4-) and DNP anion, but not FCCP anion. Thus, in contrast with mammalian mitochondria, T. pyriformis mitochondria cannot rapidly supply the cytosol with ATP; possibly the cells need high intramitochondrial ATP. The difference between DNP and FCCP is hypothetically explained by low Delta psi value and/or an increase in concentration of long-chain acyl-CoAs, inhibitors of the ATP/ADP-antiporter. The first suggestion is confirmed by absence of mitochondria with bright fluorescence in T. pyriformis stained with the Delta psi-sensitive probe MitoTracker Red. These data suggest that T. pyriformis cells are useful as a model for study of mitochondrial role in adaptation at the intracellular level.