[Conformational analysis of anti-arrhythmia agents of the lidocaine series and a model for the mechanism of their action]. / Konformatsionnyi analiz antiaritmikov lidokainovogo riada i model' mekhanizma ikh deistviia.

After conformation analysis of a number of lidocaine-like antiarrhythmic molecules a simple model of their mode of action is suggested. It is proposed that the hydrophobic antiarrhythmic molecules after their absorption on cytoplasmic membranes concentrate due to polar interactions close to ionic channel proteins, then bind to these proteins and allosterically influence the process of ionic conductance.

[Comparative studies of the antiarrhythmic activity of prolonged action quaternary ammonium derivatives of trimecaine (G-104) and lidocaine (QX-572)]. / Sravnitel'nye issledovaniia protivoaritmicheskoi aktivnosti dlitel'no deistvuiushchikh chetvertichnykh ammonievykh proizvodnykh trimekaina (Zh-104) i lidokaina (QX-572).

The antiarrhythmic activity of quaternary ammonium derivatives of trimecaine (G-104) and lidocaine (QX-572) was studied on models of arrhythmias induced in dogs by coronary artery occlusion and strophanthin intoxication and in rats by intravenous administration of aconitine. It was found that the antiarrhythmic activity and duration of action of G-104 exceed those of QX-572. The data obtained by the method of electromagnetic flowmetry showed that G-104 in doses of 0.3 and 1 mg/kg produces insignificant changes of hemodynamic parameters. By its action on transmembrane ion currents, G-104 is close to quinidine-like agents.

[Possible mechanism of long-term anti-arrhythmia and local anesthetic effect of quaternary ammonium compounds]. / O vozmozhnom mekhanizme dlitel'nogo antiaritmicheskogo i mestnoanesteziruiushchego deistviia chetvertichnykh ammonievykh soedinenii.

In experiments with dialized neurons of L. stagnalis mollusc the recovery of Na-current (INa) after its depression by local anesthetic trimecaine and its quaternary derivative N-ethyltrimecaine (G-88) was studied. A full recovery of INa within tens of seconds after washing off trimecaine but not G-88 was observed. The half-time for vanishing of INa use-dependent depression by G-88 was 17 minutes, and there was no substantial vanishing of tonic INa block even after an hour of G-88 washing off. A hypothesis is advanced that the long recovery time of INa is one of the mechanisms providing long pharmacological action of quaternary antiarrhythmic and local anesthetic ammonium compounds.

[Conformation analysis and structure-activity correlations of various lidocaine-like anti-arrhythmia agents]. / Konformatsionnyi analiz i korreliatsionnoe sootnoshenie struktura-aktivnost' nekotorykh potentsial'no aktivnykh antiaritmikov lidokainovogo riada.

Structure-activity correlationship of some potential-activity antiarrhythmic agents of lidocaine-like substances is found. Conformational properties of molecules of the substances are studied.

[Different sensitivities of two mechanisms of excitation waves in heart tissue to anti-arrhythmia agents--blockers of fast sodium currents]. / Raznaia chuvstvitel'nost' dvukh mekhanizmov tsirkuliatsii volny vozbuzhdeniia v serdechnoi tkani k antiaritmikam--blokatoram bystrogo natrievogo toka.

In experiments with rabbit ventricular tissue sensitivity of two kinds of spiral wave sources of excitation to fast sodium current inhibition was compared. These spiral wave sources were circulation in a ring around an obstacle and circulation in tissue without an obstacle (reverberator). It was observed that after application of antiarrhythmic drugs lidocaine or mexiletine there was a prominent growth of cycle length of reverberator during first few seconds of circulation and a little change of cycle length for the circus movement around obstacle. It is proposed that different sensitivity of both kinds of spiral wave sources to antiarrhythmic drugs can be used for their distinguishing in clinical practice.

[Possible mechanism of the stimulation of cell proliferation by different damaging agents]. / O vozmozhnom mekhanizme stimulirovaniia proliferatsii kletok razlichnymi povrezhdaiushchimi vozdeistviiami.

A hypothesis is advanced in which an intracellular Ca2+ increase is proposed as a common mechanism for induction of cell proliferation by different injuring influences.

[Effect of trimecaine, ajmaline, stenopril and chloracizine on fluctuations in K+ currents in rat liver mitochondria]. / Deistvie trimekaina, aimalina, stenoprila i khloratsizina na kolebaniia potokov K+ v mitokhondriiakh pecheni krys.

Antianginal hypotensive preparations chloracyzin and stenopryl, antiarrhythmic aimalin as well as local anesthetic and antiarrhythmic trimekaine hydrochloride were studied for their effect on the K+ inflow and outflow rate in the rat liver mitochondria during Sr2+-induced vibrations. In spite of differences in the chemical structure and pharmacological effect, all these substances are shown to uniformly suppress ion flow vibrations in mitochondria, inhibiting K+ outflow. It is found that the inhibition of the K+ outflow rate depends on the concentration of the preparations. Activity of the studied substances as to inhibition of K+ outflow from mitochondria correlates with their pharmacologic activity.

[Refractory properties of cardiac tissue at fast sodium current decrease. Comparison of atrium and ventricle]. / Refrakternost' serdechnoi tkani pri umen'shenii bystrogo vkhodiashchego Na-toka. Sravnenie predserdiia i zheludochka.

Investigation of the membrane potential of Neurospora crassa mycelial cells was carried out by standard microelectrode technique. The resting potential is equal to--156 +/- 11 mV (negative inside the cell). The light of the spectrum blue-violet zone causes transient hyperpolarization of the cell membrane reaching --38 +/- 5 mV after 25 minutes of illumination.

[Mechanisms of differences of the cycle length of excitation spiral waves in atrial and ventricular tissues]. / Issledovanie mekhanizma razlichnogo povedeniia perioda spiral'nykh voln vozbuzhdeniia v predserdii i zheludochke.

Ectopic spiral wave sources--reverberators--were produced in pieces of rabbit atrium and ventricle by an induction of a single properly timed premature impulse. It was found that the cycle length (T) of the ectopic source gradually increased immediately after its appearance in atrial and changed a little bit after its appearance in ventricular tissue. Relationship between changes of T and refractorines of the heart tissues was investigated. The model is proposed which explains these changes of T by the cycle length dependence on the value of fast inward sodium current.

[Refractoriness of cardiac tissue and mechanism of destruction of sources of spiral waves of excitation in the heart]. / Refrakternost' serdechnoi tkani i mekhanizm gibeli istochnikov spiral'nykh voln vozbuzhdeniia v serdtse.

Ectopic spiral wave sources were produced in pieces of 15 X 15 mm of rabbit atrium by an induction of a single properly timed premature impulse. The cycle length of the ectopic source (T) gradually increased immediately after its appearance. It was shown that T growth is determined by the rise of refractoriness (R). It was found that besides the well known phenomenon of R shortening after f increase there is an opposite process of R lengthening at high driving rates (f > 4--5 sec--1). A hypothesis is advanced that the growth of refractoriness found is one of the death mechanisms of spiral wave ectopic sources in the heart.

On the distribution and packing of RNA and protein ribosomes.

From the analysis of the measured radii of gyration of the RNA (Rg = 6.6 +/- 0.3 nm) and protein (Rg = 10.2 +/- 0.5 nm) components of the 50-S subparticle of Escherichia coli ribosomes it is concluded that proteins containing a large amount of hydrodynamically bound water are located on the periphery of the tightly packed RNA. We found that the common features of the measured X-ray scattering curves of the E. coli 70-S ribosome, its 30-S and 50-S subparticles and wheat 80-S ribosomes in the region of scattering angles corresponding to scattering vectors mu from 1 to 5 nm-1 reflect features of the RNA compact packing. A hypothesis is proposed that the compact packing of RNA helices in the range of Bragg distances of 4.5--2.0 nm is a general structural feature of all ribosomal particles.

Joint use of light, X-ray and neutron scattering for investigation of RNA and protein mutual distribution within the 50S subparticle of E. coli ribosomes.

The values of the RNA and protein radius of gyration obtained in these studies corroborate the conclusion reported earlier [1] that on average the RNA is nearer to the center of the particle than is the protein. (It should be noted for comparison that the minimal Rg value of the RNA corresponding to its dense packing as a sphere in the center of the 52S subparticle is 49 A.) Moreover, such a great difference in the radii of gyration of RNA and protein implies a definite scheme of mutual RNA and protein arrangement in the 50S subparticle -- namely the distribution of the greater mass of proteins on the RNA surface.