Antiischemic activity of new domestic antioxidant 3-hydroxypyridine etoxidol derivative.

Experiments on rats with myocardium infarction showed that intravenous administration of etoxidol in a dose of 14.2 mg/kg restricted the size of necrosis area and reduced the ratio of necrosis/ischemia zones. The test compound reduced the risk of rhythm and conduction disturbances induced by administration of toxic epinephrine doses to the mice, and increased mouse survival. Etoxidol administered intravenously to cats with acute myocardial ischemia reduced epinephrine concentration and intensity of free radical oxidation in zones of myocardial lesions against the background of the increase in norepinephrine concentration and antioxidant activity in the myocardium. By antiischemic and antioxidant activity, etoxidol was superior to its structural analogue mexidol.

[Efficiency of etoxidol in treating cardiovascular disorders caused by experimental cerebral ischemia].

A complex pharmacological study of the new cytoprotector drug etoksidol in animals with the disturbances of cerebral blood circulation showed that the intravenous introduction of the drug restores autonomous nomotopic driver of rhythm, conductivity in the atria and atrioventricular connection, and refractoriness of the atrioventricular connection, which were violated a result of sharp cerebral ischemia. The new drug does not suppress the inotropic function of the heart in cats and limits the dimensions of the zone of necrosis in rats with the myocardial infarction on the background of deficiency of the cerebral blood flow.

[The mechanism of antiarrhythmic action of a new ammonium derivative of lidocaine (LKhT-12-02)].

The results of electrophysiological investigation of the effects of LKhT-12-02 (a quaternary ammonium derivative of lidocaine) on the intact cat heart and the isolated ion channels of Lymnaea stagnalis snail showed that this compound belongs to class 1B antiarrhythmic agents (Vaughan - Williams classification). The drug does not suppress the automatic nonmonotonic rhythm driver, does not influence the conductance in ventricles, auricles, and atrioventricular node in the sinus rhythm, and does not elongate the effective refractory period of the auricles and atrioventricular node. LKhT-12-02 decreases the rate of fast depolarization of the action potential, while not reducing its duration. The compound does not influence the conduction of sodium ion channels.

[The efficacy of oxynicotinic acid a nd its derivatives in respect of functional activity of hepatocytes during acute toxic hepatopathy].

Hepatoprotective activity of oxynicotinic acid and its derivatives XC-2, XC-2, XC-4, XC-9 in destructive processes in the liver induced by CCl4 injection has been studied. It was found in that injection of oxynicotinic acid derivatives in toxic lesion of the liver decreases cytolysis, cholestasis, hepatodepressive and mesenchymal-inflammatory syndromes. Membrane-stabilizing and antioxidant effects of oxynicotinic acid derivatives increase in the following sequence: XC-1 --> XC-2, XC-3 --> XC-4, mexidol --> XC-9.

[Time course of relationships of some pathogenetic factors in acute myocardial infarction in rats]. / Dinamika vzaimosviazi nekotorykh patogeneticheskikh faktorov v ostrom periode infarcta miokarda u krys.

The correlation was examined between the ischemic and necrotic areas, the extent of necrosis, pulmonary tissue edema and duration of early postocclusive arrhythmias in the first 4 hours after coronary occlusion in rat experiments. An hour following coronary ligation, the ischemic area was shown to determine the sizes of a necrotic area, duration of early postocclusive arrhythmias and pulmonary tissue edema. Two hours after myocardial infarction simulation, there was a correlation between the sizes of a ischemic area and pulmonary tissue edema. Four hours after coronary occlusion, the edema of pulmonary tissues was closely related to the sizes of a form necrotic area.

[Mechanisms of the development of strophanthin hypersensitivity in experimental myocardial infarct and its pharmacological correction]. / Mekhanizmy razvitiia giperchuvstvitel'nosti k strofantinu pri éksperimental'nom infarkte miokarda i ee farmakologicheskaia korrektsiia.

The tolerance changes to strophanthin in cats were studied during 7 days after occlusion of the coronary artery along with the determination of the electrolyte concentration in different areas of the myocardium. It is shown that the acute disorder of the coronary circulation produces during 2 days considerable decrease of tolerance to the cardiotoxic action of strophanthin, which correlates with the electrolyte imbalance in the ischaemic and the adjacent areas of myocardium. Pharmacological analysis with the use of medicinal agents, possessing different properties established that the hypersensitivity to strophanthin in experimental myocardial infarction is an integral result of the influence of a number of factors, which when taken into account permit selection of rational medicinal correction of this phenomenon in different periods of acute myocardial ischaemia.

[Effect of fructose-1,6-diphosphate on the size of the necrotic area and course of the acute period of experimental myocardial infarction in rats]. / Vliianie fruktozo-1,6-difosfata na razmery zony nekroza i techenie ostrogo perioda éksperimenta'lnogo infarkta miokarda u krys.

The experiments on rats indicated that fructose-1,6-diphosphate substantially decreased the sizes of a necrotic zone, elevated myocardial ATP levels, reduced the edematization of lung tissue, shortened the duration of early postocclusive arrhythmias, and increased the latent period for their development. A dose-dependent cardioprotective effect was found in the preparation.

[Factors that provoke strophanthin poisoning and its drug prevention]. / Faktory, provotsiruiushchie intoksikatsiiu strofantinom i ee farmakoprofilaktika.

The effect of various pathogenic factors and drugs on sensitivity to strophanthin and the possibility of pharmacoprophylaxis of toxicosis caused by this cardiotonic agent were studied in acute and chronic experiments on 375 cats. It is shown that impaired blood supply to the myocardium, toxic affection of the liver, sensitization with the cardiac antigen, and the effect of inflammation mediators, mineralocorticoids, and some antianginous agents reduce strophanthin tolerance. The altered sensitivity to strophanthin is successfully corrected with the beta-adrenoblocker alpheprol, hydrocortisone, analgin, dimedrol, and the anesthetic trimecaine.

[A comparative evaluation of the cardioprotective and antianginal actions of energy-providing agents]. / Sravnitel'naia otsenka kardioprotektornogo i antianginal'nogo deistviia nekotorykh énergoobespechivaiushchikh sredstv.

The limitation of a myocardial necrotic area by some energy-yielding compounds in rat coronary occlusion and their capacity to elevate the ischemia threshold in conscious rabbits were studied. Sodium malate, ascorbic acid and phosphoenolpyruvate were demonstrated to reduce the sizes of necrotic areas and increase the ischemia threshold, whereas cytochrome C and fructose-1,6-diphosphate were effective solely in limiting the infection area. It was concluded that the preventive antianginal effect of energy-yielding and electron-accepting compounds depended on their capacity to accumulate in intact cardiomyocytes.

[The cardioprotective action of preparations of biotechnological cytochrome c in acute myocardial ischemia]. / Kardioprotektornoe deistvie preparatov biotekhnologicheskogo tsitokhroma c pri ostroi ishemii miokarda.

The cardioprotective effect of cytochrome c preparations was evaluated according to the test for restriction of the size of the myocardial infarct and the effect on the course of acute myocardial ischemia in acute experiments on dogs. Cytochrome c of biotechnological and animal origin and hemtetradecapeptide caused a marked decrease in the size of the myocardial necrosis in experiments on rats: from 68 +/- 4.3% in the control to 32 +/- 3.4, 46 +/- 8.3 and 44 +/- 4.7%, respectively. In dog experiments the cytochrome c agents reduced the intensity of dp/dt decline and decreased the collateral coronary blood flow in acute myocardial ischemic. They produced a beneficial effect on heart bioenergetics, namely, reduced the lactate level in blood flowing from the zone of the ischemia and glucose consumption by the ischemic myocardium. The cardioprotective effect of biotechnological cytochrome c hemtetradecapeptide was practically identical to the effect of the enzyme of animal origin.

[The spectrum of the anti-ischemic activity of immobilized cytochrome c]. / Issledovanie spektra protivoishemicheskoi aktivnosti immobilizovannogo tsitokhroma c.

The antihypoxic, anti-ischemic and antianginal activity of biotechnological cytochrome c which had been immobilized on a dialdehydedextran and polyethyleneglycol carriers was studied in various experimental animals (mice, rats, rabbits). The immobilized cytochrome c exhibits higher antihypoxic and anti-ischemic activity on different models compared to cytochrome c.

[The anti-arrhythmia activity of energy-providing and electron-acceptor compounds]. / Protivoaritmicheskaia aktivnost' nekotorykh énergoobespechivaiushchikh i élektronaktseptornykh soedinenii.

The protective effects of fructose-1, 6-diphosphate, sodium malate and cytochrome C were studied in the experiments on rats with disorders of the cardiac rhythm of various origin. The compounds studied prevent the strophantine and adrenaline-induced cardiac rhythm disturbances, but appeared ineffective on aconitine and calcium chloride models.

[The antiarrhythmic activity of glycolysis and Krebs cycle intermediates in early occlusion and reperfusion arrhythmias in rats]. / Issledovanie protivoaritmicheskoi aktivnosti nekotorykh intermediatov glikoliza i tsikla Krebsa pri rannikh okkliuzionnykh i reperfuzionnykh aritmiiakh u krys.

Acute experiments on unconscious rats have demonstrated that fructose-1,6-diphosphate, phosphoenolpyruvate and malate of sodium produced a marked antiarrhythmic activity in acute occlusive and reperfusion arrhythmias, prevented the development of ventricular fibrillation and tachycardias, considerably reduced the duration of arrhythmia paroxysms, but they were ineffective in ventricular extrasystole.

[Effect of the beta-adrenoblocker alpheprol and the alpha-adrenolytic tropaphen on tolerance to strophanthin in experimental myocardial infarct]. / Vliianie beta-adrenoblokatora alfeprola i alpha-adrenolitika tropafena na tolerantnost' k strofantinu pri éksperimental'nom infarkte miokarda.

The tolerance to strophanthin was studied in acute and subacute experiments on 76 cats at varying time after occlusion of the coronary artery branch. The beta-adrenoblocker alpheprol completely smoothed away the hypersensitivity to strophanthin after the coronary blood flow cessation while the alpha-adrenolytic tropaphen virtually did not affect the tolerance to strophanthin in intact animals even after experimental myocardial infarction.

[The effect of phosphoenolpyruvate on the course of the acute period in experimental myocardial infarct]. / Vliianie fosfoenolpiruvata na techenie ostrogo perioda éksperimental'nogo infarkta miokarda.

It was found in the experiments on dogs, that phosphoenolpyruvate decreased the level of regional metabolic acidosis, stabilized energy metabolism, cardiohemodynamics and enhanced the blood supply of the ischemic myocardium. Anti-ischemic effect of the phosphoenolpyruvate was more significant in comparison with fructose-1,6-diphosphate in isomolar doses.

[The differential indicator method of determining the areas of ischemia and necrosis in experimental myocardial infarct in rats]. / Differentsial'nyi indikatornyi metod opredeleniia zon ishemii i nekroza pri éksperiemntal'nom infarkte miokarda u krys.

Valid method for estimation of relationship between ischemic and infarct sizes was elaborated. The method is based on separate determination of Evans blue and formazan in injured and intact areas of myocardium for later calculation of myocardial ischemic and necrotic zones. The procedure ensures high level of accuracy and reproducibility of experimental data because of intrinsic control.

[Correction of hypersensitivity to strophanthin in experimental myocardial infarction by pharmacologic effects on extracardiac innervation]. / Korrektsiia giperchuvstvitel'nosti k strofantinu pri éksperimental'nom infarkte miokarda farmakologicheskimi vozdeistviiami na ékstrakardial'nuiu innervatsiiu.

Experiments on 176 cats with experimental myocardial infarction were made to study alterations in ouabain tolerance under pharmacological effects on extracardial innervation. It was shown that elimination of sympathetic innervation at different levels by benzohexonium, ornid and anapriline, as well as its relative weakening by proserine favoured the correction of hypersensitivity to ouabain in acute myocardial ischemia. Potentiation of sympatic effects by ephedrine and abolition of parasympathetic innervation by atropine increased ouabain cardiotoxicity.

[The antiacidotic and cardioprotective effects of fructose-1,6-diphosphate and dehydroascorbic acid]. / Antiatsidoticheskii i kardioprotektivnyi éffekty fruktozo-1,6-difosfata i degidroaskorbinovoi kisloty.

The antiacidotic and cardioprotective effects of dehydro-L-ascorbic acid and fructose-1,6-diphosphate were compared in experiments of rats. It was found that the both compounds exhibit the antiacidotic effect on the model of metabolic acidosis in the isolated hypoxic heart, decrease the excess-lactate degree, increase ATP level in the myocardium and reduce the size of the necrosis area 4 hours after the modelling of myocardial infarction. The significance of the antiacidotic component in the mechanism of the cardioprotective action of the energy-supplying agents is concluded.