[Various aspects of increased resistance of the brain tissue and its vessels to extreme effects with the use of GABAergic compounds and Ca(2+) antagonists]. / Nekotorye aspekty povysheniia rezistentnosti mozgovoi tkani i ee sosudov k ékstremal'nym vozdeistviiam s pomoshch'iu GAMK-ergicheskikh veshchestv i antagonistov Ca(++).

Experiments on rats showed that the morpho-functional state of the cerebral cortex microcirculatory bed suffers marked changes in different periods of hypokinesia. This was accompanied with obvious morphological changes in the brain, the development of brain edema in particular. It was found that the GABAergic agents which we used ranked below Ca-antagonists in antiedemic activity.

[The effect of verapamil on changes in the Ca2+ content of the intracellular structures of organs during acute myocardial ischemia]. / Vliianie verapamila na izmenenie soderzhaniia Ca2+ vo vnutrikletochnykh strukturakh organov v period ostroi ishemii miokarda.

In experiments on rats with acute myocardial infarction induced by occlusion of the left coronary artery in conscious animals the protective effect of verapamil on the heart, brain, liver, and kidneys in this disease was studied. The effectiveness of the drug was judged by the changes in the 45Ca2+ content in the intracellular structures (cytosol, mitochondria, endoplasmic reticulum) of the organs under study. A single injection of 200 micrograms/kg verapamil in acute myocardial infarction reduces considerably the content of 45Ca2+ in the intracellular structures of these organs and thus prevents the development of pathological processes.

[The neurotropic and cardiotropic properties of new amino acid derivatives of isonicotinic acid]. / Neirotropnye i kardiotropnye svoistva nekotorykh novykh aminokislotnykh proizvodnykh izonikotinovoi kisloty.

Different derivatives of isonicotinic acid are used widely enough as antimicrobial and antituberculous agents. However, their neurotropic and cardiotropic effects have been studied little. The paper is concerned with investigations of these types of the activity of the new derivatives of isonicotinic acid: beta-phenyl-beta-alanine, l-proline, DL-valine, beta-alanine and DL-threonine synthesized for the first time at the Institute of Fine Organic Chemistry, Academy of Sciences of Armenia.

[The antiarrhythmic action of piracetam]. / Nekotorye aspekty antiaritmicheskogo deistviia piratsetama.

It was found that a drug of the nootropic nature piracetam possessing pronounced antihypoxic properties eliminates calcium chloride-induced disturbances of the cardiac rhythm and significantly raises the threshold of atrial fibrillation during electrical stimulation. The drug's antiarrhythmic effect is followed by a decrease of the rhythm rate and an increase of the contraction amplitude. The animals treated with piracetam in a dose when its antiarrhythmic effects (300 mg/kg) exhibited a decrease of the membrane potential of erythrocytes as compared with control. Similar effects occurred in the animals treated with lidocaine. It can be concluded that in certain types of arrhythmias the use of piracetam restores the normal rhythm of contractions that is perhaps connected with its positive influence on metabolic processes in the myocardium.

Chronopharmacology of strophanthin and inderal: an experimental study.

Chronopharmacological investigations were performed in 54 guinea pigs and 126 white mice to explore their tolerance to arrhythmogenic and lethal doses of strophanthin, and changes in sensitivity to threshold antiarrhythmic dose of inderal during 24 hours. The investigations were carried out at a 4-hour interval, i.e., six times in 24 hours. The data obtained were processed using the approximation method to determine sinusoid fluctuations with an initially given period (cosinor analysis) and with an unknown period (non-linear least-square method in combination with the method of gradual approximation) on an EC 1045 computer and a DZ 28 microcomputer. It was found that strophanthin toxicity in guinea pigs and white mice reaches a maximum in the late evening, night and early morning hours. The acrophases of circadian rhythms of chronotolerance to the threshold arrhythmogenic dose of strophanthin, and those of chronosensibility to inderal are virtually identical.

[Antisoporific and cardiotropic properties of new amino acid derivatives of nicotinic acid]. / Antisnotvornye o kardiotropnye svoistva nekotorykh novykh aminokislotnykh proizvodnykh nikotinovoi kisloty.

On the models of urethane, nembutal and ethyl alcohol sleep it was shown that nicotinoylcapronate, nicotinoylserine and nicotinoylvaline possess antihypnotic properties being superior to those of cordiamine and on some models phenamine. Nicotinoylvaline and nicotinoylalanine normalized the myocardial contraction in animals with experimental ischemia.

[Effect of indomethacin on the sensitivity of the adreno- and cholinoreceptors in the cardiovascular system]. / Vliianie indometatsina na chuvstvitel'nost' adreno- i kholinoretseptorov serdechno-sosudistoi sistemy.

The effect of indometacin, an anti-inflammatory agent and prostaglandin biosynthesis inhibitor, on the sensitivity of cardiovascular adreno- and cholino-receptors was studied in anesthetized cats. 30-40 mg/kg of intraperitoneal indometacin reduced considerably alpha-adrenoceptor reactivity and increased beta-adrenoceptor sensitivity to exogenous mimetics. The drug effects on cholino-receptors are diverse and not always pronounced.

[Effect of verapamil on the molecular characteristics of myocardial actomyosin in experimental ischemia]. / Vliianie verapamila na molekuliarnuiu kharakteristiku aktomiozina miokarda pri éksperimental'noi ishemii.

Verapamil was shown to be able to recover a significantly depressed actomyosin ATPase activity of the unaffected left ventricular area in experimental myocardial ischemia. The drug also increased Ca-sensitivity of the ATPase reaction, with the amount of actomyosin components (Tn-1, LCM-1, LCM-2, Tn-C) almost reaching the control level. The possibility of direct interaction of verapamil with Ca-binding sites on actomyosin macromolecule is suggested. Its influence on metabolism and gene expression is not excluded.

[Pyromecaine--a new anti-arrhythmia preparation improving myocardial blood supply]. / Piromekain--novyi antiaritmicheskii preparat, uluchshaiushchii krovosnabzhenie miokarda.

Pyromecaine is a local anesthetic used for surface anesthesia. Its marked antiarrhythmic activity has been established in various models of experimental cardiac arrhythmia in doses of 0.1-2.5 mg/kg. Pyromecaine has a wide spectrum of antiarrhythmic action, exerts a favourable effect on the intracardiac and systemic hemodynamics, on the contractility of the left ventricle and on the myocardial blood flow following the ligation of the coronary artery. Other positive properties of pyromecaine include its anesthetic activity and a relatively low toxicity.

[Relation between extra- and intracardiac anti-strophanthin properties of anti-arrhythmic agents]. / Sootnoshenie ékstra- i intrakardial'nykh antistrofantinovykh svoistv antiaritmicheskikh veshchestv.

Animal experiments have shown that beta-adrenoblockers have the most marked antistrophanthin properties while antiarrhythmic agents with locally anesthetic attributes are less active. All the substances studied have proved to be ineffective on the cellular model of strophanthin arrhythmia. The data obtained suggest that the antiarrhythmic effect of the substances under study including beta-adrenoblockers is exercised on the level of the receptor apparatus of the postsynaptic membrane. The membrane stabilizing properties do not play the decisive role in ensuring the antiarrhythmic effect in strophanthin arrhythmia.

[Anti-arrhythmia properties of pyromecaine]. / Antiaritmicheskie svoistva piromekaina.

Antiarrhythmic activity of the local anesthetic pyromecaine has been studied. The drug has been shown to eliminate flutter of the atria provoked by electrical stimulation of the myocardium, by aconitin, strophanthine and barium chloride. It prevents ventricular fibrillation arising due to calcium chloride poisoning. The drug exhibits marked antiarrhythmic properties. It is similar to lidocaine but less toxic and has a broader therapeutic range. It does not produce any adverse action on myocardial contractility or conduction. Pyromecaine has been demonstrated to exert appreciable antiarrhythmic activity in patients. The Pharmacological Committee of the USSR Ministry of Health approved pyromecaine for use in medical practice as an antiarrhythmic drug.

[Molecular mechanisms of action of ethpenal]. / Nekotorye molekuliarnye mekhanizmy deistviia étpenala.

The effect of a new cholinolytic drug ethpenal, that is applied clinically as an antiparkinsonian and antiulcer agent, on the course of experimental myocardial infarction has been studied. The experiments have shown that in the test animals (white rats and rabbits) with myocardial infarction, ethpenal increases by 9.3% the contractile function of myofibrils, makes tissue respiration return to normal, and approximates the P/O magnitude to the control level. Administration of ethpenal to the animals with experimental myocardial infarction induces a considerable increase in the content of polyglycerophosphatides, which, in its turn, leads to stabilization of the cellular membranes. The drug improves permeability of the bilayer lecithin membranes by calcium ions. A conclusion is made that the myocardial infarction, ethpenal exerts a beneficial effect on the processes occurring at a level of the cellular membranes.

[Anti-arrhythmic activity of trimecaine under experimental and clinical conditions]. / Protivoaritmicheskaia aktivnost' trimekaina v eksperimente i klinike.

The antiarrhythmic properties of trimecaine, a local anesthetic, were studied. Tests on cats and rats with arrhythmia induced by stimulation with electric current and injection of aconitine, barium chloride, and calcium chloride as well as on a cell model of aconitine arrhythmia have shown that trimecaine possesses marked antiarrhythmic properties. It is more active and less toxic than procainamide hydrochloride or quinidine. Oral administration of 0.35% trimecaine solution had a favourable therapeutic effect in extrasystole in patients with complex heart valvular diseases and circulatory disorders. It is presumed that parenteral injection will produce a more rapid and prolonged antiarrhythmic effect.

[Role of surface phenomena in the mechanism of action of antiarrhythmic substances]. / Rol' poverkhnostnykh iavlenii v mekhanizme deistviia protivoaritmicheskikh veshchestv

The surface activity of the antiaarhythmic drugs and their influence on the lipid-containing interphasics were studied. It was found that drug No. 7351 (diphenyl isopropyl acetic acid diethyl aminopropyl ester), fubromegan, metamysil, propranolol, quinidine, novocalinamide, xylocaine, and trimecaine possessed surface activity. There exists a symbate relationship between the surface and especially the interphasic activity and the antiarrhythmic effect. The most active antiarrhythmic drug No. 7351 increased the electric conductivity of the lecithine bilayer membrane much more than novocainamide.

Mechanism of cardiotonic action of monoethanolamine and its activity in experimental myocardial hypertrophy.

The authors investigated the cardiotonic effect of monoethanolamine (MEA) and its influence on experimental cardiac hypertrophy in albino rats. In isolated hearts, myocardial cells, and glycerinized fibres as well as in the whole organism of the animals, a distinct cardiotonic effect on MEA was observed, which was most marked in pathological states of the organism. In rats with experimental coarctation of the aorta, MEA dosed 10 mg/kg stimulated, and dosed 60 mg/kg, inhibited the development of myocardial hypertrophy, while the myocardial contractility remained sufficiently preserved. The mechanism of cardiotonic action and the inhibitory effect on the development of myocardial hypertrophy at the dosage of 60 mg/kg are apparently connected with the participation of MEA in tissue metabolic processes contributing to a normalization of tissue respiration, oxidative phosphorylation, and activation of phosphatide-generating reactions, especially to the formation of phospholipids containing ethanolamine, which represent one of the most important membrane formations and components of numerous enzymic systems.

[Cholinoreception of chick embryo myocardial explants]. / Izuchenie kholinoretseptsii éksplantatov miokarda kurinogo émbriona

The effects of acetylcholine, subecholine (selective nicotinomimetic) and methylfurmetide (selective muscarinomimetic) on the spontaneous contractions of atrial and ventricular explants from the heart of 408 day embryos as well as of mixed explants, have been studied by means of a special photoelectric device. In most of the experiments, acetylcholine reduced the rate of contractions, the sensitivity of preparations being increased with the age of embryos. Preliminary atropine treatment reversed or significantly decreased acetylcholine effect. Subecholine usually increased the contraction rhythm, whereas methylfurmetide decreased the spontaneous activity.