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.

Clinical and experimental study of antiarrhythmic and antianginal effects of quaternidine.

High antiarrhythmic activity of a new Russian antiarrhythmic drug quaternidine in ventricular arrhythmia was studied in 96 coronary patients by Holter monitoring, bicycle ergometry, and echocardiography. The drug had a positive impact on local kinetics in left-ventricular ischemic myocardium and some parameters of bicycle exercise test. The preparation possesses no arrhythmogenic effect. Experiments on 30 random-bred rats showed that the drug reduced the necrotic zone under conditions of experimental coronary occlusion. Experiments on 14 intact cats demonstrated that quaternidine had no effect on coronary bloodflow.

[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.

[The effect of fructose-1,6-diphosphate and phosphoenolpyruvate on the course of early occlusion and reperfusion arrhythmias in rats]. / Vliianie fruktozo-1,6-difosfata i fosfoenolpiruvata na techenie rannikh okkliuzionnykh i reperfuzionnykh aritmii u krys.

Fructose-1,6-diphosphate (150 and 50 mg/kg) and phosphoenolpyruvate (0.5 and 0.1 mg/kg) decreased the development of ventricular tachycardia, ventricular fibrillation and the intensity of ventricular extrasystoles after coronary occlusion in experimental rats. Both compounds were active as anti-fibrillation agents on reperfusion arrhythmias. Fructose-1,6-diphosphate potentiated the effect of lidocaine.

[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.

[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.

[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 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.

[The characteristics of the cardioprotective action of fructose-1,6-diphosphate]. / Osobennosti kardioprotektornogo deistviia fruktozo-1,6-difosfata.

The cardioprotective effects of fructose-1,6-diphosphate (FDP) were investigated in infarcted rats and in conscious rabbits with myocardial ischemia. The influence of FDP on metabolic acidosis was studied in isolated hypoxic rat hearts. It was shown that FDP did not change the threshold of the initiation of ischemia in conscious rabbits, but decreased necrotic zone in infarcted rat hearts. After administration of FDP the myocardial contractility was prolonged significantly as compared with control under conditions of severe metabolic acidosis. However, FDP was not effective in hypoxic hearts with compensated metabolic acidosis. It was considered, that FDP influenced only ischemic myocytes with the changes in sarcolemmal permeability.

[The effect of Krebs cycle intermediates on the size of the necrotic zone and on the course of early postocclusion arrhythmia in experimental myocardial infarct in rats]. / Vliianie intermediatov tsikla Krebsa na razmery zony nekroza i techenie rannikh postokkliuzionnykh aritmii pri éksperimental'nom infarkte miokarda u krys.

The differential indicator method of determining the zone of myocardial ischemia and necrosis was used to show that sodium succinate and malate (100 and 200 mg/kg) significantly decrease the size of the necrotic zone in the acute period of myocardial infarction and alleviate the course of early postocclusion arrhythmias. The dose-dependent cardioprotective effect of sodium malate was noted.