[Redistribution of myocardial blood flow in chronic ischemia under the effects of pharmacological agents]. / O pereraspredelenii krovotoka v serdechnoi myshtse v usloviiakh khronicheskoi ishemii pod vliianiem farmakologicheskikh sredstv.

In the experiments with anesthetized dogs under chronic myocardial ischemia the effect of propranolol, diltiazem, lithium and sodium hydroxybutyrate on the myocardial blood flow redistribution was studied with the help of ultrasonic method. The redistribution was estimated by the ratio change of blood flows in veins which drain blood directly from the focus of myocardial ischemia and total myocardial of left ventricular (v cardiac magna). It was established that propranolol increases the ratio and diltiazem decreases it. Some differences in the effect of antihypoxic drugs were revealed. Sodium hydroxybutyrate redistributed the blood flow in favour of the focus of myocardial ischemia and lithium hydroxybutyrate increased the blood flow both in the focus of myocardial ischemia and in the conditionally-intact region of myocardium of left ventricular.

[The antifibrillatory properties of bonnecor]. / Protivofibrilliatornye svoistva bonnekora.

The preventive and therapeutic effects of bonnecor were shown in the experiments on awake and anesthetized rats under conditions of acute myocardial ischemia. It was concluded that the relieving influence of bonnecor on the course of acute myocardial ischemia was related to its antifibrillatory and antiarrhythmic properties.

[The effect of bonnecor on cardiac hemodynamics, blood supply and function in experimental myocardial ischemia]. / Vliianie bonnekora na gemodinamiku, krovoobrashchenie i funktsiiu serdtsa pri éksperimental'noi ishemii miokarda.

The effect of a new antiarrhythmic drug bonnecor on the hemodynamics, blood supply and function of the ischemic heart as compared with the famous antiarrhythmic drugs lidocaine and ethacizine was studied in the experiments on anesthetized animals (rats, dogs) under artificial respiration. It was shown that bonnecor administered in a dose of 0.5 mg/kg was able of relieving disturbances of the cardiac hemodynamics and function produced by occlusion of the coronary artery. The drug exerted no significant effect on the blood supply to the focus of acute and chronic myocardial ischemia.

[Bonnecor--a new anti-arrhythmia preparation]. / Bonnekor--novyi antiaritmicheskii preparat.

The antiarrhythmic properties of a new drug bonnecor being a derivative of dibenzazepine were studied on different models of arrhythmias. Bonnecor proved to be effective in the treatment of both atrial and ventricular arrhythmias of various genesis except rhythm disorders induced by ouabain intoxication. The drug was shown to exert a pronounced antifibrillatory effect and to increase the electrical stability of the intact and ischemic myocardium.

[The anti-arrhythmia properties of bonnecor metabolites]. / Antiaritmicheskie svoistva metabolitov bonnekora.

The experiments on the model of aconitine-induced arrhythmia in anesthetized rats and awake dogs with cardiac rhythm disorders caused by the coronary artery occlusion showed that all four metabolites of bonnecor possessed the antiarrhythmic activity. Metabolite 4 proved to be the most active on both models of cardiac rhythm disorders.

[A comparative study of the pharmacokinetics and pharmacodynamics of bonnecor]. / Sravnitel'noe izuchenie farmakokinetiki i farmakodinamiki bonnekora.

The pharmacokinetics and pharmacodynamics of bonnecor were studied simultaneously in animals with experimental arrhythmia. It was shown that irrespective of the animal species and individual features of the drug elimination kinetics the level of bonnecor concentration correlated with the antiarrhythmic effect. The data on the excretion of bonnecor and its metabolites in the urine in the dog and man were obtained. The decrease of bioavailability at oral administration of bonnecor was demonstrated to be related to its intensive conversion in metabolite M-I.

[Quantitative assessment of the blood supply to the focus of myocardial ischemia in dogs in pharmacological research]. / Kolichestvennaia otsenka krovosnabzheniia ochaga ishemii miokarda u sobak v farmakologicheskikh issledovaniiakh.

The method of quantitative evaluation of blood supply of ischemic myocardial focus was suggested, it consists in measuring the venous blood outflow from the ischemic area with the help of ultrasonic technique. In experiments on anaesthetized dogs with coronary artery occlusion the rate of blood flow and dynamics of its changes in the ischemic focus were determined. It was shown that sodium oxybutyrate improves the blood supply of myocardial ischemic area.

[Anti-arrhythmia and antifibrillatory properties of dibenzazepine derivatives]. / Antiaritmicheskie i antifibrilliatornye svoistva proizvodnykh dibenzazepina.

Antiarrhythmic and antifibrillation properties of bonnecor, a derivative of dibenzepin, were studied in comparison with ethmozine, quinidine and novocainamide, using various experimental arrhythmia models. Bonnecor activity was somewhat smaller than that of ethmozine, and much greater than that of quinidine and novocainamide in the mixed atrioventricular arrhythmia model simulated in aconitin-treated rats and the ventricular arrhythmia model simulated by two-degree coronary occlusion in dogs. Intravenous 1 mg/kg and oral 6 mg/kg bonnecor doses prevented ventricular fibrillation caused by acute coronary occlusion in rats, while ethmozine showed no such effect.

[Ethacizin: pharmacologic properties and prospects for clinical application]. / Etatsizin: farmakologicheskie svoistva i perspektivy klinicheskogo primeneniia.

The study of the regularities between the chemical structure and pharmacologic action of phenathiazine dialkylaminoacyl derivatives led to the identification and investigation of a new drug called ethacizine-phenothiazin-2-carbethoxyamino-10 (beta-diethylamino-propionyl) hydrochloride. Ethacizine exceeds its structural analogue ethmozin by two times in terms of intensity and by 4-5 times in terms of the duration of antiarrhythmic effect. Ethacizine has marked antianginal properties. It shows a prolonged inhibitory effect on the average elevation of the ST interval at multiple leads of the epicardial electrogram during coronary occlusion, increases the threshold of myocardial ischemia development, and reduces the size of experimental infarction. The combination of potent antiarrhythmic activity, already confirmed by clinical observations, with antianginal properties and a capacity to limit the size of infarction makes in possible to consider ethacizine a promising means for treating coronary heart disease.

[Interaction of nonachlazine and noradrenaline on a model phospholipid membrane]. / Vzaimodeistvie nonakhlazina i noradrenalina na model'noi fosfolipidnoi membrane

The binding of nonachlazine (NCL), imipramine (IMP), and noradrenaline (NA) with the model phospholipid membrane vesicles--liposomes--was studied. The binding was determined by the qunching effect of these substances on the fluorescence of 3-methoxybenzantrone (MBA) present in the membrane of the fluorescent probe. A method rendering possible calculation of the binding of the preparations under study with the membrane of the basis of the fluorescence changes was developed. The binding constant of the NCL, IMP, and NA interaction with the membrane was equal to (4.3 +/- 0.3)-10(3)M-1, (2.7 +/- 0.2)-10(3)M-1, and (0.7 +/- 0.15)-10(3)M-1, respectively. It was shown that NCL and IMP could compete with NA for the membrane binding centers. Such competitive interactions could be regarded as a probable mechanism of the block of the reverse NA transport through the synaptic and the vesicular membranes characteristic of NCL and IMP.

[Effect of nonachlazine on the processes of uptake and release of nordrenaline]. / Vliianie nonakhlazina na protsessy zakhvata i vysvobozhdeniia noradrenalina.

Nonachlazine (2 micrometer) blocked significantly the uptake 1 of endogenic noradrenaline in the myocardial tissues and in adrenergic neurons of vas deferens. The uptake II, as well as the intensity and dynamics of the noradrenaline release were not affected by nonachlazine. These processes resulted in an increase of free noradrenaline concentrations in the synaptic space. The latter seems to be a result of the mediator's passage into the nerve fibers (through axonal membranes) and into the granule, this being due to the nonachlazine-induced block. It is suggested that the metabolic and functional nonachlazine effects are related to the beta-adrenergic receptors stimulation, mediated through the agency of noradrenaline.

[Analysis of the effect of morphine and promedol on uptake and release of noradrenaline by myocardial tissue]. / K analizu vliianiia morfina i promedola na zakhvat i vysvobozhdenie noradrenalina tkan'iu miokarda

A study was made of the effect of morphine and promedol on the content, uptake, and release of norepinephrine (NE) on rat myocardium. Promedol proved to decrease the NE level in the myocardium. Morphine failed to influence the release of the NE-14C from the isolated perfused heart, whereas promedol increased it significantly, altering both the "slow" and the "rapid" release of the mediator. Promedol failed to influence the uptake of NE-14C by the perfused heart, whereas morphine decreased it significantly. The competition between morphine and NE was characterized by the effect of incomplete inhibition: morphine and NE produced reciprocal effects on the affinity of one another to the receptor, and their interaction depended on the ratio of the concentrations of these drugs.