[Action of ethacizin on normal and anomalous forms of Purkinje fiber automaticity in the dog]. / Deistvie étatsizina na normal'nuiu i anomal'nye formy avtomatii volokon Purkin'e sobaki.

The effect of a new anti-arrhythmic drug etacysin was studied in various forms of dog Purkinje's fibres automativity: normal and abnormal arising at a late stage of experimental myocardial infarction (24 hrs after coronary artery ligation) and induced by ions Ba2+. An average 57% decrease in the frequency of automaticity of normal Purkinje's fibres due to steepening the slope of slow diastolic depolarization and almost complete depression of an abnormal one was observed for the drug concentrations 5 X 10(-7) and 10(-6) g/ml. Reduced automaticity was also related to decreased slow diastolic depolarization. Maximal values of diastolic potential were found unchanged.

[Decrease in the fast sodium inflow current, a possible reason for the anti-arrhythmic action of etmozin and mexityl in the late stage of experimental myocardial infarct]. / Umen'shenie bystrogo vkhodiashchego natrievogo toka--vozmozhnaia prichina antiaritmicheskogo deistviia étmozina i meksitila v pozdnei stadii éksperimental'nogo infarkta miokarda.

Ethmozine (1--2 mg/kg, i. v.), mexiletine (2--8 mg/kg, i. v.), and tetrodotoxin (TTX) (0.5--3.0 g/kg, i. v.) reduced ventricular arrhythmias occurring 24 hours after ligation of the coronary artery in dogs. Simultaneous infusion of subthreshold doses of ethmozine and TTX or mexiletine and TTX reduced ventricular arrhythmias to the same degree as infusion of threshold doses of either agent alone. TTX, therefore, potentiates the antiarrhythmic effect of ethmozine and mexiletine. Since TTX blocks the fast sodium current specifically, this finding suggests that the antiarrhythmic effect of ethmozine and mexiletine in the late stage of myocardial infarction is due to the inhibition of the fast inward sodium current.

[Effect of the diethylamine analog of etmozin on myocardial function (a clinical and experimental study)]. / Vliianie diétilaminovogo analoga étmozina na funktsional'noe sostoianie miokarda (kliniko-éksperimental'noe issledovanie).

Diethylamine analogue of ethmozine (DAA ethmozine) administered intravenously in the doses of 0.5-1 mg/kg exerts marked antiarrhythmic effect both experimentally and clinically, slight effect on the arterial pressure and myocardial contractility and led to insignificant and to statistically insignificant depression of automatism of the sinus node and on the fibres of the conductive system. DAA ethmozine enhanced the duration of the refractory periods of atriae and of the atrio-ventricular node by 20-30%, increased the time of stimulation conduction at all the levels of the conductive system of the heart. Sensitivity of the rapid sodium channels to DAA ethmozine exceeded by one order their sensitivity to ethmozine proper. The sum total of the results and also the preliminary data on the high antiarrhythmic activity of DAA ethmozine justifies the conclusion that this drug may prove to be effective in the treatment of cardiac arrhythmias.

[Comparison of the intensity of the effect of ethmozine and its diethylamine analog on the ectopic foci of excitation at the late stage of experimental myocardial infarct]. / Sravnenie intensivnosti deistviia etmozina i ego diétilaminovogo analoga na éktopicheskie ochagi vozbuzhdeniia v pozdnei stadii éksperimental'nogo infarkta miokarda.

The atrioventricular block was produced in dogs 24 hours after the occlusion of the left descending coronary artery by formalin injection into the atrioventricular node or the bundle of His. The intensity and duration of the ectopic foci inhibition produced by ethmozine and by its diethylamine analogue (ethmozine DAA) were compared. It was shown that intravenous infusion of 3 mg/kg ethmozine reduced the frequency of the ectopic ventricular excitations by 28% (n = 6), 0.5 mg/kg ethmozine DAA - by 46% (n = 7), and 1 mg/kg ethmozine DAA - by 78% (n = 8). In 50% of the animals 1 mg/kg ethmozine DAA completely suppressed the ectopic activity. Duration of the drugs action was determined by the time necessary for the attainment of 50% of the maximal effect in the inhibition of ectopic exitation frequency (for 3 mg/kg ethmozine it was 32.7 +/- 2.5 min, for 0.5 mg/kg ethmozine DAA - 5.1 +/- 7.2 min, and for 1 mg/kg ethomozine DAA - 55.0 +/- 9.8 min). The results obtained suggest that the ethmozine DAA action is more intensive and of longer duration than ethmozine, and effective at the late stage of experimental myocardial infarction.

[Circulatory responses to selective stimulation of medullated and non-medullated fibers of the aortic nerve]. / Reaktsii krovoobrashcheniia na izbiratel'nuiu aktivatsiiu menliniziro vannykh i nemielinizirovannykh volokon aortal'nogo nerva.

Circulatory responses to selective afferent stimulation of medullated and non-medullated fibers in the left aortic nerve were followed in terms of changes in arterial pressure, heart rate, contractile force of the left ventricular fragment and vascular resistance of the hind limb of cats with an opened thorax. Stimulation of the medullated afferents induced a reflex fall of blood pressure mainly by means of decrease in the peripheral vascular resistance, while activation of non-medullated fibers influenced the heart work, i. e. decreased heart rate and myocardial contractile force.

[Anti-arrhythmic effect of tetrodotoxin in the late stage of experimental myocardial infarct]. / Antiaritmicheskoe deistvie tetrodotoksina v pozdnei stadii éksperimental'nogo infarkta miokarda.

The action of tetrodotoxin (TT), blocking the fast sodium current, on arrhythmias that occurred 24 hours after occlusion of the coronary artery was studied in 10 dogs. TT injected intravenously in doses of 0.5--3.0 micrograms/kg significantly decreased the number of ventricular extrasystoles, and completely restored sinum rhythm in 4 animals. The maximum antiarrhythmic effect was noted 3 to 5 minutes after TT adminstration. It is suggested that arrhythmias and the antiarrhythmic effect of the drugs in the late stage of myocardial infarction are connected with the fast inward sodium current.

[Effect of tetrodotoxin and ethmozine on arrhythmias of a dog heart isolated in the late stage of experimental myocardial infarct]. / Vliianie tetrodotoksina i étmozina na aritmii serdtsa sobaki, izolirovannogo v pozdnei stadii éksperimental'nogo infarkta miokarda.

Dog hearts with ventricular extrasystole that developed 24 hours after coronary artery occlusion were isolated and perfused with blood from support dogs. After heart isolation the rhythm disturbances persisted regardless the decreased frequency of the ventricular beats. Administration of tetrodotoxin (4 X 10-8--10-7 g/ml) and ethmozine (3--5X X10-5 g/ml) abolished ventricular arrhythmias and restored the sinus rhythm. Potential mechanisms of the increased susceptibility of ischemic myocardial fibers to tetrodotoxin and antiarrhythmic drugs are discussed.

[Effect of the diethylamine analog of etmozin and cesium chloride on the idioventricular rhythm in dogs in the late stages of experimental myocardial infarct]. / Vliianie diétilaminovogo analoga étmozina i khlorida tseziia na idioventrikuliarnyi ritm u sobak v pozdnei stadii éksperimental'nogo infarkta miokarda.

Atrioventricular block was produced by infusion of 0.1-0.2 ml of 40% formaline into the A-V node or the bundle of His. Effect of diethylamine analog of etmozin (1 mg/kg) and cesium chloride (20 mg/kg) on the idioventricular rate was studied in control and experimental dogs 24 hours after the occlusion of the coronary artery. It was shown that cesium ions inhibit the idioventricular rate in the normal canine heart (from 49.9 +/- 3.8 to 6.9 +/- 4.5/min; p less than 0.001, n = 7) and have no influence on the ectopic ventricular rate in the late stage of myocardial infarction. On the contrary, diethylamine analog of etmozin has no significant effect on normal ventricular automatism and considerably reduces the ectopic ventricular rate (from 111.5 +/- 7.2 to 23 +/- 15.6/min; p less than 0.001, n = 8). The evidence points to the difference between the ionic mechanisms determining the normal specialized conduction system automatism and the ionic mechanisms which are responsible for the enhanced automatism in the late stage of experimental myocardial infarction.