[Radio Frequency Electromagnetic Field Effect on the State of Na+/Ca2+ Exchange in the Isolated Rat Heart].

It has been shown that a single exposure to 171 MHz electromagnetic field with 180 V/m electric field strength and 0.04 mW/kg specific absorption rate significantly alters the Na+/Ca2+ exchange in the isolated rat heart. It is assumed that enhancement of the Na+/Ca2+ exchange towards removing Ca2+ from the cardiomyocytes electromagnetic field exposure is a result of Ca2+ extraction from the sarcoplasmic reticulum and the increase of its intracellular level.

[The influence of application of a low-frequency magnetic field on the serum corticosterone level (an experimental study)].

The results of analysis of the literature publications suggest the necessity of experimental studies aimed at investigation of modulating effect of low-frequency magnetic fields on endocrine organs. The present study was carried out using 200 outbred white male rats (body weight 200-220 g). Corticosterone was measured in blood sera following the application of a low-frequency magnetic field (20 and 53 Hz with induction from 0.4 to 6 mT) generated by a Mini-Expert-T apparatus for induction magnetic therapy during 30 minutes. It was shown that the application of the alternating magnetic field to the adrenal region of the rats in the selected frequency and induction ranges caused a significant increase in the serum corticosterone levels. The results of the present study on the hormonal activity of rat adrenals give reason to consider the influence of the alternating magnetic fields as being modulatory. Analysis of the data thus obtained has demonstrated the non-linear dependence of glucocorticoid activity of the rat adrenal glands on the induction strength of the alternating magnetic field.

[The mechanisms of the effect of a high extracellular sodium concentration on the contractile activity of the isolated rat heart]. / Mekhanizmy vliianiia vysokoi vnekletochnoi kontsentratsii natriia na sokratitel'nuiu aktivnost' izolirovannogo serdtsa krys.

Increase in the extracellular concentration of sodium (from 140 mM to 200 mM) causes an initial increase in the developing left-ventricular pressure which is replaced by increase of the amplitude of contractions by 40-50% in comparison with the initial condition. Lithium chloride (60 mM) did not cause similar changes. The initial diminution of myocardial contractility under the effect of a hypersodium medium was not sensitive to verapamil, ethmosin, lidocaine, caffeine or the Na-H exchange blocker hexamethylenamyloride (HMA). Verapamil (0.1 microM) or HMA (1 microM) did not influence the increase in the developing pressure induced by the hypersodium medium. The favorable inotropic effect of the hypersodium medium was manifested after arrest of the heart with verapamil (2 microM). Caffeine (2 microM), ethmosin (1 microM) or lidocaine (100 microM) weakened the favorable effect of the hypernatrium medium.

[The anti-arrhythmia properties of thymogen]. / Antiaritmicheskie svoistva timogena.

The antiarrhythmic and antifibrillary effects of thymogen were determined by using 6 models of arrhythmias induced by aconitine, calcium chloride, strophanthin, low-sodium, reperfusion, and epinephrine. The dose-response curve was examined. The mechanism of thymogen's action was also studied.

[The effect of thymogen on the heart in ischemia and reperfusion]. / Vliianie timogena na sostoianie serdtsa pri ishemii i reperfuzii.

The anti-ischemic properties of thymogen were studied on an isolated heart model. Its cardioprotective effect was higher than that of dalargin and verapamil. The mechanism of the thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.

[The effect of a number of pharmacological preparations on Na-H metabolic activity and on the passive permeability for protons of the sarcolemma of the isolated heart]. / Vliianie riada farmakologicheskikh preparatov na aktivnost' Na--H-obmena i passivnuiu pronitsaemost' sarkolemmy izolirobvannogo serdtsa dlia protonov.

The influence of the local anesthetics hydrocortisone hemisuccinate and peptide drugs (thymogen and dalargin) on Na-H exchange activity and passive proton permeability of the sarcolemma was studied in experiments on isolated rat hearts. It was established that neither local anesthetics or hydrocortisone hemisuccinate, nor peptide drugs affected Na-H exchange activity. Lidocaine (5 mM), procaine (5 mM), hydrocortisone hemisuccinate (500-750 mg/l) inhibited sarcolemmal passive proton permeability by 40-70%. Aetaphone in the micromolar range attenuated the role of these effects in the antiarrhythmic action of local anesthetics and aetaphone.

[Effect of sodium and magnesium ions on development of a "calcium paradox" in cardiac muscle]. / Vliianie ionov natriia i magniia na razvitie "kal'tsevevogo paradoksa" v serdechnoi myshtse.

The isolated rat heart was used to examine the impact of ion concentrations of sodium ions in the Ca-free medium on the development of cardiomyocytic damage after the former sodium ion concentration had been restored in the solution (the calcium paradox). Lowering a concentration of sodium ions in the Ca-free medium was found to enhance the development of the calcium paradox if the perfusion media contained no magnesium ions. Adding magnesium (0.125-1.2 mM) throughout the experiment reversed the action of the decreased sodium medium and contributed to the preservation of high concentrations of energy-rich compounds, to that of mitochondrial conjugation of oxidation and phosphorylation, to more than 4-fold cardiac release of myoglobin. An artificially elevated sodium ion concentration (as high as 170-220 mM) was effective in preventing cardiac energy impairments irrespective of the magnesium ion concentration. The positive action of the unchanged concentration of sodium ions during the calcium paradox was completely reversed by strophanthin. The findings are in a good agreement with the so-called sodium hypothesis of calcium paradox development.

[Relation between the energy state and permeability of cardiomyocyte sarcolemma during "calcium paradox" and activity of glycolysis]. / Zavisimost' énergeticheskogo sostoianiia i pronitsaemosti sarkolemmy kardiomiotsytov pri "kal'tsievom paradokse" ot aktivnosti glikoliza.

Reperfusion by Ca(2+)-containing solution after 10 minutes of Ca(2+)-depletion resulted in the loss of myoglobin, depletion of ATP and phosphocreatine (calcium paradox). Exhaustion of high energy phosphates exacerbated when glucose was substituted by pyruvate or acetate. Iodoacetate (30 mcM) elevated loss of myoglobin due to calcium paradox. Addition of 120 mM glucose reduced loss of myoglobin and depletion of high energy phosphates after induction of the calcium paradox. There is a close correlation between concentration of lactate and ATP in the hearts subjected to calcium paradox. Elevated activity of glycolysis protected hearts against the calcium paradox.

[Effect of a sodium transmembrane gradient on efflux of creatinine from the myocardium]. / Vliianie transmembrannogo gradienta natriia na vykhod kreatina iz miokarda.

Heart maintains a gradient for creatine under physiological conditions, so that creatine release is relatively small. Calcium depletion, addition of strophanthin or decrease of sodium concentration (till 80 mM) provoke release of creatine. Elevation of transmembrane sodium gradient by raising of extracellular sodium concentration prevented loss of creatine. The effect of elevated concentration of sodium ions was blocked by strophanthin but depended on osmolarity, because solutions with the same osmolarity that hypersodium media had no protective effect on release of creatine. A sarcolemmal mechanism of Na creatine cotransports is proposed.

[The role of ion transport system of sarcolemma in amino acid loss during myocardial perfusion with calcium-free medium and myocardium injury during "calcium paradox"]. / Rol' ionotransportnykh sistem sarkolemmy v potere aminokislot pri perfuzii serdtsa beskal'tsievoi sredoi i povrezhdenii miokarda pri "kal'tsievom paradokse".

The loss of myocardial amino acids is known to depend on sodium gradient across sarcolemma. This is regulated by changes of cellular volume as well. It is suggested that loss of amino acids can be regulated by blocking of anion-transporting systems during Ca-free perfusion. It have been found that calcium depletion from extracellular medium exacerbates release of amino acids two- four fold. Sodium lowering (from 140 mM to 30 mM) accelerates and sodium elevation (from 140 mM to 200 mM) attenuates loss of taurine, glutamine, glycine, glutamate, aspartate, alanine and asparagine, but does not hydrophobic amino acids. Inhibition of CI- channels by IAA94 or K-Cl cotransport with DIOA increases the loss of taurine, glutamine, glycine, glutamate, aspartate, alanine and asparagine during Ca-free perfusion. The release of amino acids during Ca-free perfusion is negatively correlated with recovery of oxidative phosphorylation during the second phase the calcium paradox-Ca-readmission.

[Effect of extracellular concentration of sodium on swelling of cardiomyocytes and myocardial damage during calcium paradox]. / Vliianie vnekletochnoi kontsentratsii natriia na velichinu nabukhaniia kardiomiotsitov i povrezhdenie cerdtsa pri "kal'tsievom paradokse".

The aim of investigation was to study the effects of extracellular sodium concentration on cardiomyocyte swelling and evaluation of this process in myocardial damage due to the calcium paradox. The experiments on isolated rat hearts showed that reperfusion by Ca- containing solution (Ca2+ 2.0 mM) after 10 minutes perfusion with Ca- free medium caused ameliration of water contents, depletion of high-energy phosphates, loss of myoglobin and uncoupling of respiration and phosphorylation in mitochondria. Either decreasing of sodium concentration (till 30-80 mM) or addition of strophant-hine (50 microM) resulted in exacerbation of calcium paradox (further augmentation of tissue water contents and increasing of cellular damage). Sucrose (240-340 mM), added low-sodium Ca- free solution was failed to prevent accumulation of water, loss of myoglobin and high- energy phosphates caused by subsequent perfusion with Ca- containing medium. Elevation of extracellular concentration of sodium ions (from 140 mM till 200-220 mM), but did not tonicity reduced cellular swelling, water accumulation in tissue, prevented loss of myoglobin and ATP, phosphocreatine level. The protective effect of hypersodium medium remained unchanged even sucrose was added to reperfusion solution to maintain osmotic pressure throuthout experiment. There are close correlation between intensity of water accumulation and degree of myocaridal damage during the calcium paradox, that confirms participant of Na- dependent cellular swelling in the development of cellular abnormalities due to calcium paradox.

[Effect of antioxidant histochrome preparation on the contractile function and metabolism of the isolated rat heart under conditions of "calcium paradox", ischemia, and reperfusion]. / Vliianie antioksidantnogo preparata gistokhrom na sokratitel'nuiu funktsiiu i metabolizm izolirovannogo serdtsa krysy v usloviiakh "kal'tsievogo paradoksa", ishemii i reperfuzii.

A comparative study of protective effect of a new antioxidant histochrome on isolated rat heart at calcium paradox and ischemia-reperfusion was carried out. Perfusion with Ca-containing solution after 10-min perfusion with Ca-free medium caused depletion of high energy phosphates, loss of myoglobin, uncoupling of mitochondria, increase of left ventricular diastolic pressure. Pretreatment with histochrome led to decrease of cardiomyocyte damage evaluated by myoglobin efflux in perfused solution, attenuation of decrease ATP and phosphocreatine, and coupling of mitochondria. This resulted in a decrease of left ventricular diastolic pressure at calcium paradox. Less effect of histochrome treatment was noted in the case of ischemia-reperfusion model. It was concluded that histochrome effectively prevents heart from abnormalities caused by calcium imbalance in heart.

[A decrease in cardiac sensitivity after ischemia to a change in the extracellular concentration of calcium ions]. / Snizhenie chuvstvitel'nosti serdtsa posle ishemii k izmeneniiu vnekletochnoi kontsentratsii ionov kal'tsiia.

Reperfusion of the heart 30 min. after ischemia causes slight recovery of contractility and content of macroergic compounds in the myocardium tissue. Recovery of perfusion by the hypercalcium medium (0.05 mol/l) improves metabolism of the myocardium 30 min after ischemia. However, further perfusion by solution with physiological content of Ca2+ is followed by the development of the myocardium contracture, essential decrease in extracellular concentration of ATP and phosphocreatine. An increase in the extracellular sodium concentration and addition of macroergic compounds (ATR, phosphocreatine) adenosine, when reperfusing the heart by hypocalcium solution, improve the postischemic state of the myocardium and protect it from injuries during the following recovery of physiological Ca2+ content in the extracellular medium.

[The prevention of the development of myocardial contracture in the "calcium paradox" by action on Na-Ca metabolism]. / Preduprezhdenie razvitiia kontraktury miokarda pri "kal'tsievom paradokse" vozdeistviem na Na--Ca-obmen.

The effect of artificial high sodium gradient on the rate of the myocardium contracture development during "calcium paradox" was studied in the experiments on the isolated heart of Langendorf-perfused rats. It is stated that artificial creation of a high sodium gradient decreases the rate of the myocardium contracture development. Exogenous nucleotides, activators of Na, K-ATPase, and their precursors intensified the protective action of the hypersodium medium. Phosphocreatine (100 mmol/l) had no protective effect during the "calcium paradox". However, under conditions of the high sodium gradient phosphocreatine efficiently prevented development of the contracture during the "calcium paradox". It is important to note that under analogous conditions creation of high osmosity of the solution adding 12 mmol/l of saccharose does not protect the heart from development of the myocardium contracture.

[Prevention of myocardial reperfusion injury by increasing artificial trans-membrane sodium gradient in "calcium paradox" and post-ischemic reperfusion]. / Preduprezhdenie iskusstvennym uvelicheniem transmembrannogo gradients natriia reperfuzionnykh povrezhdenii cerdtsa pri "kal'tsievom paradokse" i postishemicheskoi reperfuzii.

An effect of the high sodium gradient during "calcium paradox" and postischemic reperfusion has been studied. A decrease of Na/Ca exchange by high sodium gradient (200 mM NaCl in the perfusion solution) resulted in the reduction of myoglobin release from the heart during "calcium paradox". High sodium concentration solution (200 mM) increased protective effect of ATP during "calcium paradox". Exogenous phosphocreatine (100 mumol/mol) increased myoglobin release from the heart. During perfusion of the heart by high sodium concentration, phosphocreatine efficiently decreased myoglobin release from the heart during "calcium paradox". Exogenous ATP (as Na-pump activator) and high Na+ concentration solution (180 mM) prevented the LDH release from the myocardium, decreased ATP hydrolysis, inhibited Ca influx, maintained total adenine nucleotides, phosphate potential, energy charge of the cardiomyocytes.

[Amiloride decreases heart susceptibility to "calcium paradox" after total ischemia]. / Amilorid umenshaet chuvstvitelnost serdtsa k "kaltsievomu paradoksu" posle totalnoi ishemii.

It is shown that reperfusion of the postischemic heart by low-calcium solution and standard media was accompanied by a massive release of myoglobine, contracture development without cardiac contractions. Addition of amiloride (35 mmol/1) 5 min before ischemia and during low-calcium reperfusion prevents the heart damage after reintroduction of the standard-calcium media. We consider that high susceptibility of the postischemic heart to calcium paradox can be explained by activation of Na/H exchange and a decrease in the sodium gradient during low-calcium reperfusion. These findings confirm the so-called "intracellular sodium" hypothesis of the calcium paradox.

[Dependence of myocardial contracture on energy resources during the calcium paradox]. / Zavisimost' kontraktury miokarda pri "Kal'tsievom paradokse" ot énergeticheskikh resursov.

Perfusion of the rat isolated hearts with calcium-free and calcium containing solution revealed a complex and deep myocardial damage called the calcium paradox. The reperfusion of the rat heart with calcium rich media resulted in myoglobin loss from the heart, significant decreasing of ATP and phosphocreatine level, complete uncoupling of respiration and phosphorylation in mitochondria, occurrence of myocardial contracture. Decreasing of sodium level to 30 mM--80 mM in calcium free media exacerbates the heart damage due to the calcium paradox with absence of contracture. Addition of phosphocreatine (1 mM, 5 mM, 10 mM) evoked some restoration of ATP contents in the tissue with appearance of significant contracture. Phosphocreatine exacerbated the loss of myoglobin from the heart subjected to the calcium paradox. A discrepancy between myocardial contracture and degree of cellular damage has been observed during the calcium paradox.

[The protective action of adenosine in the development of the "calcium paradox" in the isolated heart]. / Zashchitnoe deistvie adenozina pri razvitii "kal'tsievogo paradoksa" v izolirovannom serdtse.

Calcium repletion (2.0 mM) after 10 min of calcium depletion (pCa = 7) resulted in the loss of myoglobin, decreased contents of ATP and adeninucleotides. Adenosine in concentration 50-1000 mcM depressed the release of myoglobin and prevented depletion of ATP and adenine nucleotides during the "calcium paradox". Theophylline, a non-selective A1-receptors blocker did not alter either "calcium paradox" development or protective effect of adenosine. Dipiridamole, an inhibitor of transmembrane transport of adenosine, protected hearts against the "calcium paradox" depending on the concentration. Dipiridamole (50 mcM) abolished protective effect of high concentrations (100-1000 mcM) of adenosine. The results obtained prove that transmembrane transport of adenosine is more important than its interaction with receptors for its protective effect under the "calcium paradox".

[Metabolism of extracellular phosphocreatine during changes in the ionic composition of the medium in the perfused rat heart]. / Izuchenie metabolizma vnekletochnogo fosfokreatina pri izmenenii ionnogo sostava sredy v perfuziruemom serdtse krys.

Perfusion of isolated rat hearts with a phosphocreatine (10(-4) M) containing solution to which strophanthin or KCl had been added up to a concentration of 27 mM as well as Ca2+ depletion decreased phosphocreatine concentration in the perfusate with a simultaneous increase in creatine and phosphocreatine concentrations in the myocardium. Neither high extracellular concentrations of Na+ (200 mM), nor phosphocreatine increased creatine and phosphocreatine levels in the myocardium. The effect of high sodium perfusion media was completely reversed by strophanthin. Phosphocreatine decreased the lactate content in the perfusate. Strophanthin or potassium chloride enhanced the effect of phosphocreatine on the lactate release. Conversely, creatine augmented the lactate content in the perfusate. A high specificity of the phosphocreatine effect on the myocardium independently of the ionic composition of the perfusate was postulated. A mechanism of protective effects of phosphocreatine and high sodium perfusion media on "calcium paradox" is proposed.

[Significance of extracellular concentration of sodium ions in the protective effect during the "calcium paradox"]. / Znachenie vnekletochnoi kontsentratsii ionov natriia v osushestvlenii fosfokreatinom zashchitnogo deistviia pri "kal'tsevom paradokse".

Increasing of extracellular sodium concentration up to 200 mM diminishes heart damage under "calcium paradox". Phosphocreatine (10(-4) M) potentiates the effect of high sodium perfusion media; in this case myoglobin release from the myocardium is minimal (5-9% of control). An the same time, ATP and phosphocreatine concentrations and oxidation to phosphorylation coupling in mitochondria remain at a sufficiently high level. Elevation of osmotic pressure by the effect of 120 mM sucrose enhances heart damage under "calcium paradox" both in the presence and absence of phosphocreatine. The protective effects of superhigh (200 mM) sodium concentrations and phosphocreatine are completely reversed by strophanthin or decreasing K+ concentration down to 0.5 mM.