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Biomedical subjects

G G Beloshapko

Publications and source records attributed to G G Beloshapko.

At least 19 recordsLinked to original sources
PubMed1994

Combination ethacizin and ethmozin treatment of resistant ventricular ectopy: theoretical, experimental, and clinical study.

Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the "guarded-receptor" model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals < 600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 +/- 2% in these patients without side effects. In the "nonresistant" but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with "fast-off" and one with "slow-off" kinetics, which may provide a general rationale for choosing drug combinations.

Adult↗
PubMed1991

Influence of ionic modification on electrical activity of Purkinje fibers obtained from dogs with 1-day-old myocardial infarction.

A stable sustained rhythmic activity (SRA) occurred in 62 of 192 specimens isolated from the infarcted subendocardium of 48 dogs 24 h after a left descending coronary artery occlusion. Changes in [Na+]o and/or [Ca2+]o of the superfusate allowed us to distinguish two types of responses, suggestive of two different mechanisms for SRA. In type 1 responses at constant [Na+]o, the rate of SRA decreased when [Ca2+]o was increased and increased when [Ca2+]o was decreased. When [Ca2+]o was held constant, the rate of SRA was directly related to [Na+]o. In type 2 responses, at constant [Na+]o, the rate of SRA was directly proportional to [Ca2+]o. In contrast, at constant [Ca2+]o, SRA was inversely proportional to [Na+]o. When a constant [Ca2+]o/[Na+]o3 ratio was maintained, the type 2 response became indistinguishable from the type 1 response. The combination of lower temperature (36 degrees C) and high initial [Ca2+]o (2.7 mM) favored the type 2 response (28 of 32 preparations). In contrast, 25 of 30 preparations studied at 39 degrees C and 1.35 mM [Ca2+]o showed the type 1 response. These results suggest that SRA in the 24-h infarct model can be due to both abnormal automaticity (type 1) or triggered activity (type 2) and that changes in temperature and ionic milieu will largely determine which of the two mechanisms is responsible for SRA.

Animals↗
PubMed1991

Modulating intraventricular conduction through competition of two class 1 antiarrhythmic agents: experience with ethacizin and lidocaine in canine heart.

The frequency-dependent effects on the intraventricular conduction through the dog heart in situ produced by two class 1 antiarrhythmic drugs, ethacizin and lidocaine, with different kinetic properties were investigated. Conduction delay was measured using stimulation of the His-bundle after pharmacologically induced atrioventricular (AV) block. Electrical events were derived from local epicardial bipolar electrograms at the base of the right ventricle. The stimulation program consisted of several 50-pulse trains with progressively shorter interstimulus intervals (ISI) separated by a l-s pause. Ethacizin (1.5 mg/kg) increased conduction delay by 30% at ISI of 1000 ms, and the effect was enhanced when ISI was shortened to 200 ms; l-s pauses did not significantly increase conduction velocity. Addition of lidocaine (12 mg/kg) strongly potentiated the ethacizin effect at ISI shorter than 300 ms without any noticeable increase in conduction delay at longer intervals. The major result was dramatic acceleration of conduction during the l-s pauses while both drugs were infused. With this combination, conduction delay after pause was shorter than with ethacizin alone, which is consistent with the competition of the drugs for the same binding site inside the sodium channel. Combination of two class 1 compounds in clinical practice may enhance their antiarrhythmic effects without adversely inhibiting normal impulse conduction in the heart. Computer-predicted data were in reasonable agreement with experimental results. The "guarded receptor" model, thus, can provide a simple method for predicting local anesthetic drug interactions in man.

Animals↗
PubMed1990

[Effects of ethmozine on ventricular fibrillation threshold in acute occlusion of the coronary artery in dogs].

In experiments on dogs with acute left descending coronary artery occlusion, ethmozine (3 mg/kg) was tested for effects on the threshold of ventricular fibrillation occurring as a result of high-frequency electric stimulation. Two hours after occlusion, the fibrillation threshold became significantly lower than the control values. Ethmozine used in this period enhanced the ventricular fibrillation threshold in some experiments and diminished it in the others. Four hours following the occlusion, the fibrillation threshold did not differ from the control ones. Ethmozine given in this period caused a significant increase in the ventricular fibrillation threshold. It was concluded that 4 hours after the onset of experimental myocardial infarction are the minimal time period following which administration of ethmozine failed to decrease electric stability of the heart.

Animals↗
PubMed1990

[The combined effect of 2 first-line anti-arrhythmia drugs on the conduction velocity of myocardial stimulation].

Experiments with recording the time of intraventricular reentry of the canine heart by a special protocol of stimulation showed that the first-line antiarrhythmic agents having various kinetics, ethacizine and lidocaine, compete for their binding to the Na+ channels of cardiac fibers. As a result of this competition, additivity was not found in the effects of ethacizine, 1.5 mg/kg, and lidocaine, 12 mg/kg, on the rate of intraventricular conduction at heart rate under 180/min. At higher cardiac rhythm values, the total effects of the two agents on the conduction were observed. The experimental evidence confirm the results of mathematical modelling of the combined effects of ethacizine and lidocaine on the intraventricular conduction velocity, which were calculated on the basis of kinetic constants for binding and dissociation of the agents to Na+ channels. The findings show that when the two first-line antiarrhythmics having a substantially different kinetics were used in combination, their antiarrhythmic effect may be enhanced without their total effects on the rate of normal intraventricular conduction velocity reentry.

Animals↗
PubMed1989

[Effects of tetrodotoxin and verapamil on abnormal ventricular activity at the late stage of experimental myocardial infarction in dogs].

An in situ experimental study of the heart has demonstrated that verapamil++ (0.3 mg/kg), administered intravenously to dogs with complete transverse heart block one day after two-step occlusion of the left descending coronary artery either produced a 15-30% drop in the incidence of abnormal ventricular activity (AVA) in some experiments, or had no effect on the latter in others. Tetrodotoxin (3 micrograms/kg) produced a 20-44% drop in AVA in all experiments. Combined administration of 0.2 mg/kg verapamil++ and 2 micrograms/kg tetrodotoxin completely suppressed AVA. At an early phase of its development (5-10 hours after the occlusion of the left descending artery), AVA was completely suppressed both by 0.3 mg/kg verapamil and 3 micrograms/kg tetrodotoxin. Mechanisms of AVA and its progress following coronary-artery occlusion in dogs are discussed.

Animals↗
PubMed1988

Some mechanisms of nonspecific antiarrhythmic action of phosphocreatine in acute myocardial ischemia.

Using isotope-labeled microspheres (diameter 15 microns) it was shown that phosphocreatine at a dose of 300 mg/kg does not affect the myocardial blood flow in the ischemic zone during acute occlusion (5 min) of the left anterior descending coronary artery (LAD) in dogs. Intravenous administration of NaCl hypertonic solution which contained the same amount of Na+ as 300 mg/kg of phosphocreatinine disodium salt prevented the development of ventricular fibrillation during acute LAD occlusion in dogs. Under these conditions excitation conduction velocity significantly increased. Experiments in isolated intraventricular rabbit septum have showed that the addition of phosphocreatine or phosphocreatinine to the perfusion medium at a concentration of 10 mmole/liter increased excitation conduction velocity in ischemic myocardium. However, when changes in perfusate Na+ and Ca2+ concentration produced by addition of phosphocreatine or phosphocreatinine were compensated, these compounds do not affect excitation conduction velocity. On the other hand, the alterations similar to those produced by the addition of phosphocreatine or phosphocreatinine led to the same increase of excitation conduction velocity. The results obtained indicate an important role of the changes of blood plasma ionic composition on intravenous administration of phosphocreatine in electrophysiological and antiarrhythmic effects of this substance during acute myocardial ischemia.

Acute Disease↗
PubMed1988

[Mechanisms of the anomalous activity of the Purkinje fibers in the late stage of experimental myocardial infarct in dogs].

The anomalously active (AA) subendocardial Purkinje's fibers (PF) in the ischemic zone 24 hours after occlusion of the left descending coronary artery (LDCA) in dogs are proposed to be divided into 2 groups according to their reaction to the changes in the ionic composition of perfusion solution. The AAPF frequency in the first group decreased by increase in [Ca2+]o, increased by fall in [Ca2+]o and was proportional to [Na+]o. In the second group AAPF frequency rose under actions increasing [Ca2+]i (increase in [Ca+]o, decrease in [Na+]o), and fell under actions reducing [Ca2+]i (decrease in [Ca2+]o, increase in [Na+]o). After short-term (10 s) high frequency stimulation the AAPF frequency in the group I fibers either remained unchanged or insignificant transitory slowing down was registered. In the group II fibers the AA frequency after high frequency stimulation either remained unchanged or insignificant transitory elevation was observed. The anomalous activity in the group I fibers could be blocked by tetrodotoxin, while verapamil was practically ineffective. In the second group anomalous activity was blocked by both drugs. We conclude thus that one day after the occlusion of LDCA in the ischemic zone PF with anomalous activity caused by anomalous automaticity as well as by trigger mechanism may be present. The pacemaker current inducing anomalous automaticity is possibly caused by Na+ intake through ischemically modified natrium channels.

Action Potentials↗
PubMed1987

[The appearance and development of ventricular rhythm disorders in the 1st 24 hours after the start of experimental myocardial infarct in dogs].

The emergence of ventricular tachycardia (VT), its temporal progress and response to high-frequency stimulation were studied in 10 dogs subjected to two-step occlusion of the left descending coronary artery (LDA). Within two hours after the LDA ligation under atrioventricular block all animals developed an atrioventricular nodal rhythm of 37 +/- 9 pulses per minute that could be suppressed by high-frequency ventricular stimulation, i.e. the so-called overdrive suppression (OS) phenomenon was occurring. Three or four hours after LDA ligation, atrioventricular block brought out VT in 8 dogs. The onset of VT was always abrupt, its episodes being short-lived at first and growing progressively longer with time. Once VT was established, its rate increased gradually to reach the peak that exceed the base line VT rate by 21 +/- 9% 2 or 3 hours later. As the VT rate increased, the OS phenomenon grew less pronounced and disappeared altogether as the VT peak was reached. The results suggest that the abrupt emergence of VT 3 or 4 hours after the onset of myocardial infarction can be a result of ectopic pacemaker activity of partially depolarized fibres that in some cases may be due to the effects of a trigger mechanism.

Animals↗
PubMed1986

Effect of phosphocreatine and related compounds on the phospholipid metabolism of ischemic heart.

Changes in the content of lysophosphoglycerides in a crude plasmalemmal fraction of canine heart during short-term ischemia (occlusion of the left descending coronary artery for 8 min) have been studied in the presence and in the absence of phosphocreatine and phosphocreatinine. In the control experiments without PCr or PCr-nine ischemia caused significant elevation of the content of LPG: that of lysophosphatidylcholine was increased by 83% and that of lysophosphatidylethanolamine by 168%. Intravenous administration of PCr and PCr-nine in doses of 300 mg/kg completely prevented accumulation of LPG in the ischemic zone. Because of the well-known arrhythmogenic properties of LPG, the inhibitory effect of PCr and PCr-nine on the elevation of their concentration in the ischemic zone may be closely related to the antiarrhythmic action of PCr and PCr-nine in acute myocardial ischemia.

Animals↗
PubMed1986

Serial production of controlled periods of temporary heart block used to unmask and assess latent ventricular automaticity during experimental acute myocardial ischemia.

This study examined the onset, time course of development and response to overdrive stimulation of ventricular tachycardia in 10 dogs that underwent a Harris two-stage ligation of the left anterior descending coronary artery. Transient (12 +/- 3 minutes) complete atrioventricular (AV) block was produced 2, 3, 4, 5, 8, 12, 16, 20 and 24 hours after onset of infarction through selective injection of physostigmine salicylate into the AV node artery. Seven of the 10 dogs had early transient arrhythmic episodes that occurred within 20 to 40 minutes after coronary occlusion but none of the dogs had any spontaneous ventricular tachycardia in the ensuing 2 hours. Two hours after left anterior descending coronary artery ligation, complete AV block unmasked in every dog a slow (37 +/- 9 beats/min) AV junctional rhythm readily suppressed by overdrive. Three hours after coronary ligation, AV block revealed a monomorphic ventricular tachycardia (106 +/- 10 beats/min) in 3 of the 10 dogs. Four and five hours after coronary ligation, five and eight dogs, respectively, had ventricular tachycardia during AV block and in three the tachycardia was polymorphic. The two remaining dogs did not develop ventricular tachycardia during the 24 hours of observation. Ventricular tachycardia always began abruptly, first with brief and then longer bursts. Soon after onset the rate of tachycardia began to increase to reach a plateau 2 to 3 hours later at frequencies 21 +/- 9% greater than the initial tachycardia rate. Concomitant with this increase in rate there was a steady decline of overdrive suppressibility and during the plateau phase there was little or no overdrive suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Electrophysiological action of ethacizin in acute myocardial ischemia in dogs].

The effects of ethacizin on delayed activation of the ischemic myocardium by acute left anterior descending coronary artery occlusion were studied in dogs. Ethacizin, administered intravenously at a dose of 0.5 or 1 mg/kg depressed the conduction of excitation in the ischemic myocardium and significantly increased the incidence of ventricular fibrillation. Electrophysiological effects of ethacizin in acute myocardial ischemia, as well as its antiarrhythmic activity at the advanced stages of experimental myocardial infarction might be related to an intensive influence of ethacizin on fast inward sodium current in the myocardial fibers.

Animals↗
PubMed1985

The antiarrhythmic action of phosphocreatine in acute myocardial ischemia.

The mechanism of antiarrhythmic action of phosphocreatine on ischemic myocardium was studied by analyses of electrograms from normal and ischemic tissues. Ischemia induced significant changes in amplitude, duration, and conduction time of the electrograms, thereby showing depolarization of membranes and retarded conduction of excitation. Phosphocreatine administered in a single dose, 300 mg/kg iv, completely eliminated ventricular fibrillations in the ischemic hearts and significantly diminished the electrical instability occurring during reperfusion. The effects of phosphocreatine were completely reproduced by its structural analog phosphocreatine which is inactive in the creatine kinase reaction. It is concluded that the antiarrhythmic effect of both compounds is related to their specific chemical structure and that their specific effect is likely to be mediated via interaction with a sarcolemma site.

Animals↗
PubMed1985

[Mechanism of the anti-arrhythmic action of phosphocreatine in acute myocardial ischemia].

The association between phosphocreatine's antifibrillatory action and its effect on the excitement propagation processes in the ischemic area was investigated under acute coronary arterial occlusion in dogs. Ischemia considerably reduced the amplitude, and increased the duration and time of onset, in local electrograms, and provoked cardiac fibrillation at the time of occlusion or during the recovery of coronary flow. A single intravenous injection of 300 mg/kg phosphocreatine eliminated cardiac fibrillation and largely prevented electrographic changes in the ischemized area. Phosphocreatinine, phosphocreatine's structural analogue, produced a similar effect. It is suggested that antiarrhythmic action of phosphocreatine and phosphocreatinine is mediated by their membrane effects.

Acute Disease↗
PubMed1985

[Effect of phosphocreatine and phosphocreatinine on membrane phospholipid metabolism in acute myocardial ischemia].

The effect of phosphocreatine and phosphocreatinine on changes in crude lysophosphoglycerides (LPG) in the plasmatic membranes of canine heart, induced by short-term ischemia (an 8-minute-long occlusion of the left descending coronary artery), was examined. Ischemia caused a considerable rise in LPG level, with a mean 83% rise in lysophosphatidyl choline and a 168% rise in lysophosphatidyl ethanolamine. Intravenous administration of 300 mg/kg phosphocreatine or phosphocreatinine completely prevented the accumulation of LPG in the ischemic area. Since LPG have pronounced arrhythmogenic properties, the data obtained suggest that anti-arrhythmic activity of phosphocreatine and phosphocreatinine in acute myocardial ischemia results from the effect these substances have on membrane phospholipid metabolism in the ischemized area.

Animals↗
PubMed1982

[Effect of the diethylamine analog of etmozin on myocardial function (a clinical and experimental study)].

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.

Action Potentials↗