[Effect of echinochrom on experimental myocardial reperfusion injury]. / Vliianie ekhinokhroma na éksperimental'noe reperfuzionnoe povrezhdenie miokarda.

Echinochrom, a new antioxidant of the polyhydroxynaphthaquinone class, was tested for its cardioprotective activity in a model of occlusive reperfusion myocardial infarction (90-min occlusion and 4-hour reperfusion) in the acute experiments with open-chest dogs. The bolus intravenous injection of echinochrom in a dose of 1 mg/kg 5 min before reperfusion caused a significant (over 40%) reduction in the size of a necrotic focus. A supplementary administration of echinochrom 5 min after the onset of ischemia failed to contribute to a significant enhancement of its protective effect, suggesting that there is no substantial effect of the agent on ischemic lesion. The efficacy of echinochrom given after prolonged ischemia, low effective doses, and no adverse effects create prerequisites for using the drug in the clinical setting.

[A method of modeling of occlusion-reperfusion induced myocardial infarction and quantitative evaluation of the effectiveness of limitation of its size]. / Metod modelirovaniia okkliuzionno-reperfuzionnogo infarkta miokarda i kolichestvennoi otsenki éffektivnosti ogranicheniia ego razmerov.

An experimental mathematical model was proposed to assess the efficiency of experimental myocardial infarction (MI) size limitation. A canine model of occlusion-reperfusion myocardial lesion was used in an acute experiment with an open chest. 90-minute occlusion and 4-hour reperfusion were performed by carotid coronary bypass surgery. The necrotic zone and the risk area were visualized by double perfusion with tetrazolium staining. Retrograde coronary blood flow was used as a measure of collateral blood flow. The multiple linear regression equation with values of the risk zone and retrograde blood flow/risk area ratio used as independent variables enabled the size of myocardial infarction to be highly accurately predicted. Comparison of the true size of MI with the "expected" one provided methods for quantitative assessment of pharmacological limitation of MI sizes. Calculating an individual value for each animal made it possible to examine its relation to coronary circulation parameters and facilitated comparison of benefits from various agents.

[The effect of holotoxin A1 on transport of calcium ions across the lipid models of biological membranes]. / Vliianie golotoksina A1 na perenos ionov kal'tsiia cherez lipidnye modeli biologicheskikh membran.

Planar bilayer lipid membranes formed from trepang phospholipids possess an intrinsic Ca2(+)-permeability. These phospholipids dissolved in a non-polar solvent can extract 45Ca2+ from the aqueous to the organic phase. The triterpenic glycoside holotoxin A isolated from the trepang Stichopus japonicus inhibits the Ca2+ flux of lipid bilayers from trepang phospholipids as well as the Ca2+ flux induced in phosphatidylcholine bilayers by the calcium ionophore X-537A. Toxin inhibits the Ca2+ ionophore A23187 induced Ca2+ efflux from phosphatidylcholine liposomes and 45Ca2+ transition from the aqueous to the organic phase. Holotoxin A does not inhibit the 45Ca2+ transfer to the non-polar phase induced by holoturia phospholipids and does not affect the phosphatidylcholine hydroperoxide-induced Ca2+ flux of lipid bilayers. Using the fluorescent probe pyrene, it was demonstrated that toxin increases the microviscosity of liposomal membranes and trepang oocyte "ghosts".

[The relation of arterial pressure and the rate of Na-Li countertransport in a representative subsample of the population of Moscow residents]. / Zavisimost' mezhdu arterial'nym davleniem i skorost'iu Na-Li-protivotransporta v reprezentativnoi podvyborke iz populiatsii zhitelei Moskvy.

A study was made of the relationship between Na-Li countertransport and arterial blood pressure in 95 persons selected at random from the representative sample (n = 1716) of the population of one of the districts of Moscow. Of these, 34 persons turned out to be normotensive, 15 had borderline hypertension, 44 stable essential hypertension, and 2 persons presented with secondary hypertension. A positive correlation was found between countertransport and age and weight, determining 20.4% of interindividual variability of countertransport values. The mean value of countertransport in the hypertension group appeared much higher than in the normotensive group, both without and with regard to the correlating parameters. Repeated examinations demonstrated that the countertransport value in each person remained unchanged for two years. A nonlinear correlation was discovered between countertransport and arterial blood pressure. The rate of countertransport is not related to arterial blood pressure (low and high values). A dramatic change in the countertransport values occurred within a narrow borderline range of arterial blood pressure.

[Na-Li countertransport and the diagnosis of hypertension and combined hypertension and renal artery stenosis]. / Na-Li-protivotransport i diagnostika gipertonicheskoi bolezni, sochetaniia gipertonicheskoi bolezni i stenozov pochechnykh arterii.

The rate of Na-Li countertransport was studied in inpatients with essential hypertension (n = 59), chronic diffuse glomerulonephritis (n = 30), chronic pyelonephritis (n = 26), renovascular hypertension (n = 15) and in those with associated renovascular hypertension and essential hypertension (n = 4). Multiple regression analysis has demonstrated that age, body weight and blood plasma lipids do not make any significant contribution to dispersion of the counter transport rate. The mean rate of countertransport in patients with essential hypertension turned out much higher than that in patients with secondary hypertensions. Repeated examinations have shown that in every man, the countertransport rate remains unchanged for 1.5 yr. It is not affected either by hypotensive therapy or surgical treatment. In inpatients with secondary hypertension and low rates of countertransport, high arterial pressure (AP) drops after surgical treatment of the kidneys, renal vessels or adrenals. Surgical treatment of patients with secondary hypertension and high rates of countertransport does not lead to any material decrease of AP. It is assumed that the rate of Na-Li countertransport can be used for diagnosing associated secondary hypertensions and essential hypertension and prediction of AP lowering after surgical treatment.

[Interaction of alkali metal ions with Ca2+-binding center of Ca2+- ATPase of the sarcoplasmic reticulum in skeletal muscles]. / Vzaimodeistvie ionov shchelochnykh metallov c Ca2+- sviazyvaiushchimi tsentrami Ca2+-ATPazy sarkoplazmaticheskogo retikuluma skeletnykh myshts.

Sodium ion interaction with sarcoplasmic reticulum (SR) membranes leads to considerable alterations of the [23Na]NMR lineshape. Na+ binding to SR in the presence of Ca2+ and H+ is well described by a model which postulates a competitive ion binding to high and low affinity sites of Ca2+-ATPase. The dissociation constant, Kd, for high and low affinity sites is 5 and 10 mM, respectively, for Na+ and (3-5).10(-8) and 1.5.10(-3) M, respectively, for Ca2+. The pK value for high and low affinity sites is 7.3 and 6.1, respectively. Other alkaline metal ions compete with Na+ for the low affinity sites of Ca2+-ATPase; their affinities decrease in the following order: Na+ = K+ greater than Rb+ greater than Cs greater than Li+. Some of the Na+ binding sites (approximately 10%) do not interact with Ca2+.

[Antioxidant properties of benzofurocaine, phenycaberan and orthophen]. / Antioksidantnye svoistva benzofurokaina, fenikaberana i ortofena.

The antioxidant properties of benzofurocaine, phenycaberan, crithophen, alpha-tocopherol and ionol were evaluated by inhibition of oxygen absorption by liposomes from egg phosphatidylcholine induced by the addition of an prooxidant. The activity of the tested agents at inhibition of Fe2+-ascorbater-initiated oxidation decreases in the order: ionol, benzofurocaine, phenycaberan, orthophen, alpha-tocopherol; emine-initiated (EDTA-independent) oxidation of phosphatidylcholine is inhibited only by ionol, orthophen and alpha-tocopherol. Phenycaberan exerts no effect on oxidation and benzofurocaine increases the rate of emine-initiated absorption of oxygen. Thus, benzofurocaine, phenycaberan and orthophen may be referred to as selective inhibitors of Fe2+-initiated peroxidation of phosphatidylcholine.

[Binding of monoclonal antibodies to fragmented erythrocyte membranes in patients with arterial hypertension]. / Sviazyvanie monoklonal'nykh antitel s fragmentirovannymi membranami éritrotsitov bol'nykh s arterial'nymi gipertenziiami.

The data obtained by radioimmunoassay indicate that monoclonal antibodies (MA) to sarcoplasmic reticulum membranes can also bind to erythrocyte membranes. The binding of MA to fragmented erythrocyte membranes from patients with essential hypertension (n = 20) is 35% higher, as compared to normal subjects (n = 14) or patients with secondary (renal) hypertension (n = 9). Possible use of radioimmunoassays for MA is discussed with reference to differential diagnosis of arterial hypertensions.

[Mechanisms of the inhibition of Fe2+-induced oxidation of phosphatidylcholine by polyhydroxynaphthoquinones]. / Mekhanizmy ingibirovaniia Fe2+-indutsirovannogo okisleniia fosfatidilkholina poligidroksinaftakhinonami.

The kinetics of egg phosphatidylcholine oxidation induced by an artificial prooxidant Fe2+--ascorbate system or hematine was followed by oxygen uptake. The protective effect of natural free radical scavangers--polyhydroxynaphthoquinones, ionol (BHT), alpha-tocopherol and EDTA was estimated by the decrease of the phosphatidylcholine oxidation rate. EDTA was shown to inhibit the Fe2+--ascorbate-induced oxidation but had no effect on the hematine-induced oxidation. The inhibiting effect of polyhydroxynaphthoquinones on Fe2+--ascorbate-induced oxidation was 10-100 times as high as that on hematine-induced oxidation. The effects of BHT and alpha-tocopherol were the same in both models. Natural polyhydroxynaphthoquinones interacted with the free radical diphenylpicrylhydrazyl in stoichiometric ratios coinciding with the number of beta-hydroxyls in naphthoquinone molecules; the methylation of these hydroxyls fully suppressed such an interaction. Two possible mechanisms of action of polyhydroxynaphthoquinones as antioxidative agents are discussed. The first of these is coupled with the formation of Fe2+--PHNQ complexes, while the second one--with their effect as free radical scavengers. In both cases, beta-hydroxyls of naphthoquinone molecules were shown to play a key role.

[Effect of caffeine on the Ca2+-transport function of sarcoplasmic reticulum vesicles in the rat myocardium]. / Vliianie kofeina na Ca2+-transportiruiushchuiu funktsiiu puzyr'kov sarkoplazmaticheskogo retikuluma iz miokarda krysy.

The effects of caffeine on active transport of Ca2 by heavy and light fractions of rat myocardial microsomes were investigated with the use of a Ca2+-selective electrode and nephelometry. It was found that under the effect of caffeine (5 mM) the rate of Ca2 transport in the presence of oxalate decreased by 30 to 40%. The caffeine-induced inhibition was prevented by ruthenium and tetracaine, thus suggesting the inhibitor specificity. Since caffeine is a specific blocker of Ca2 transport to the terminal cisterns of the skeletal muscle sarcoplasmic reticulum, it is assumed that the microsomal fraction of rat myocardium contains terminal cistern fragments.

[Fractionation of fragments of skeletal muscle sarcoplasmic reticulum according to their sensitivity to caffeine]. / Fraktsionirovanie fragmentov sarkoplazmaticheskogo retikuluma skeletnoi myshtsy po ikh chuvstvitel'nosti k kofeinu.

Sarcoplasmic reticulum fragments were fractionated according to the ability of caffeine to selectively block Ca2+ uptake in the population of caffeine-sensitive membranes. The membrane suspension was loaded with calcium in the presence of oxalate, Mg-ATP and caffeine, after which the Ca2+-loaded caffeine-sensitive fragments were separated by sucrose density gradient centrifugation. In Ca2+-unloaded fragments of the supernatant, the sensitivity to caffeine estimated by its ability to diminish the rate of Ca2+ uptake, Ca/ATP ratio and Ca-oxalate capacity amounted to 91-93%. The terms of protein composition, the caffeine-sensitive fragments were identified with terminal cystern membranes, while the caffeine-insensitive ones with the SR canalicular membranes. The sensitivity to caffeine may serve as a reliable criterion for estimating the relative content of terminal cystern fragments in different microsomal preparations.

[Energy-dependent redistribution of a lipophilic anion in sarcoplasmic reticulum vesicles and Ca2-ATPase molecules]. / Energozavisimoe pereraspredelenie lipofil'nogo aniona v vezikulakh sarkoplazmaticheskogo retikuluma i molekulakh Ca2+-ATPazy.

The distribution of lipophilic anion of phenyldicarbaundecarborane (PCB-) between water phase and fragments of sarcoplasmic reticulum (SR) from skeletal muscle was studied, using a bilayer lipid membrane (BLM) as a selective electrode. Addition of ATP leads to an increase in PCB- binding to SR vesicles. The ATP effect is totally reversible only in the presence of both EGTA and A23187. Chlorides, in contrast with oxalate and phosphate, do not reduce the ATP-dependent PCB- binding. Oxalate decreases also the energy-dependent extrusion of protons from SR into the medium. Preliminary incubation of SR fragments with calcium gluconate leads to a decrease in PCB- binding. Addition of ATP to purified Ca2+-ATPase is coupled with a release of PCB- and calcium from the enzyme. It is suggested that ATP-dependent binding of PCB- to SR membranes reflects calcium incorporation into the hydrophobic region of Ca2+-ATPase molecules.

[Effect of acidosis on Ca2+ binding by the sarcoplasmic reticulum and on relaxation of the cardiac muscle]. / Vliianie atsidoza na pogloshchenie Ca2+ sarkoplazmaticheskim retikulumom i rasslablenie serdechnoi myshtsy.

A value of Ca2+ binding in 1 second by sarcoplasmic reticulum fragments from guinea pig hearts increased proportionally to elevation of Ca2+ concentration from 0.1 to 3.0(-6) M at pH 7.2. Decline of pH to 6.8 and 6.2 decreased the Ca2+ bound in 1 second, but increased the Ca2+ bound in 30 seconds when membrane permeability has become a crucial factor in determining Ca2+ bound. In experiments on guinea pig papillary muscles, a decline of pH from 7.35 to 6.83 resulted in a nearly equal fall in velocities of isometric contraction and relaxation (27 and 21%, respectively), but during isotonic shortening when the relaxation proceeds much faster, a fall in relaxation velocity (44 +/- 3%) was significantly more profound as compared to the fall in contraction velocity (29 +/- 4%). This effect as well as a decrease in initial rate of Ca2+ binding by sarcoplasmic reticulum suggest a direct inhibitory effect of acidosis on Ca2+ removal from myofibrils in myocardial cells.

[Ca2+-dependent ATPases of the sarcoplasmic reticulum of skeletal and cardiac muscles and their ion-transporting fragments]. / Issledovanie Ca2+-zavisimykh ATF-az sarkoplazmaticheskogo retikuluma skeletnoi i serdechnoi myshts i ikh iontransportiruiushchikh fragmentov.

The data are presented on fractionation of cardiac and skeletal muscle Ca2+-ATPase fragments obtained by trypsin and cyanobromide hydrolysis. Amino acid composition of Ca2+-ATPases isolated from the heart and skeletal muscles and of enzyme fragments is determined. The ionophoric properties of the intact enzyme and its fragments are studied. The low-molecular weight enzyme fragment decreases velocity and the level of Ca2+-accumulation by the vesicles of sarcoplasmic reticulum. It is suggested that an "ionphoric" fragment of muscle ATPase is able to form transmembrane Ca2+-selective channel in model lipid membranes.