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Biomedical subjects

J Toyama

Publications and source records attributed to J Toyama.

At least 145 records · Page 8Linked to original sources
PubMed1987

Competitive inhibition of cardiac sodium channels by aprindine and lidocaine studied using a maximum upstroke velocity of action potential in guinea pig ventricular muscles.

An interaction between aprindine and lidocaine on cardiac fast sodium channels was investigated in isolated guinea pig ventricular muscles. A conditioning clamp pulse was applied from -90 to 0 mV through the single sucrose gap voltage clamp, and the maximum upstroke velocity (Vmax) of action potential elicited after the clamp pulse was measured as an index of sodium channel availability. In the presence of aprindine (2 and 5 microM) or lidocaine (20 and 40 microM), Vmax of test action potential 100 msec after the clamp pulse was decreased progressively as the clamp pulse duration was prolonged. The time constant of this inactivated channel block by aprindine was much slower than by lidocaine. Vmax after a 1000 msec clamp pulse recovered exponentially with a time constant of 4.75 to 4.81 sec for aprindine and 254 to 260 msec for lidocaine. In the presence of both aprindine and lidocaine, Vmax recovered in dual exponential function, where the short and the long time constant corresponded to the values for single treatment with each drug. In preparations treated with aprindine alone the use-dependent decrease of Vmax was observed during stimulation trains at rates higher than 0.1 Hz. This use-dependent block was attenuated significantly after additional application of lidocaine resulted in a net increase in Vmax at 0.5 to 1.0 Hz. These findings suggest that aprindine and lidocaine may block the sodium channels by binding to a common receptor site with different kinetics, leading to a competitive displacement with each other at their high concentrations.

Action Potentials↗
PubMed1986

Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia.

Effects of hypoxia on atrioventricular conduction were investigated in the Langendorff-perfused isolated heart of the rabbit with various extracellular calcium concentrations ([Ca2+]) as well as in the presence of verapamil, nifedipine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) and chlorpromazine. The prolongation of the atrio-His (AH) interval by hypoxia for 7 min was greater with increasing [Ca2+]o ranging from 1.2 to 5.2 mM. At [Ca2+]o of over 3.2 mM under hypoxic conditions, AH block of the Wenckebach type was observed in some cases. Verapamil (5 X 10(-8) M) and nifedipine (5 X 10(-8) M) caused a significant prolongation of AH intervals before hypoxia. However, the intensity of AH prolongation due to hypoxia was significantly attenuated in the presence of the calcium entry blocker, and AH block was not induced even at 3.2 mM [Ca2+]o. W-7 (5 X 10(-6) M) and chlorpromazine (10(-6) M) did not affect the AH intervals before hypoxia. The hypoxia-induced prolongation of the AH interval or AH block was prevented in the presence of these drugs. W-5, a chlorine-deficient derivative of W-7, showed no protection against hypoxia-induced AV nodal conduction disturbances. These findings suggest that hypoxia-induced AV nodal conduction disturbance is explained, at least in part, by the electrical uncoupling of nodal cells, probably due to the calcium overload. This conduction disturbance is protected by calcium entry blockers or by calmodulin inhibitors, but the mode of protective action is not the same for these different categories of drugs.

Animals↗
PubMed1986

Endocardial mapping of ventricular tachycardia in one-day-old myocardial infarction.

Endocardial mapping of ventricular tachycardia (VT) was performed in one-day-old myocardial infarction using a matrix electrode (6 X 7 = 42) placed on the endocardial surface of the perfused isolated canine heart. Spontaneous focal VT was observed in all 7 dogs. It was neither affected nor terminated by electrical stimulation. Focal VT was induced in 5 dogs by constant pacing or premature programmed stimulation of the main left bundle. It was terminated by electrical stimulation and induction of the VT was suppressed by verapamil (5 X 10(-7)). Endocardial mapping of the spontaneous focal VT and induced focal VT showed initiation of activation from the surviving Purkinje fiber in the infarcted or border zone with subsequent circular expansion of excitation. Reentrant VT was induced in 3 dogs by bursts of rapid pacing and deteriorated into ventricular fibrillation. Endocardial mapping showed a continuous arc of functional conduction block and slowly circulating activation front around the block. It is suggested that in experimental one-day-old myocardial infarction VT resulted from abnormal automaticity and triggered activity in the surviving Purkinje fiber and reentry in the subendocardial muscle layer.

Animals↗
PubMed1986

[Electrophysiological effects of KW-3049, a new dihydropyridine type Ca antagonist, on isolated rabbit hearts, sinus nodal tissues and guinea-pig ventricular muscles].

Effects of KW-3049 on electrophysiological properties of the heart were examined using Langendorff-perfused hearts and superfused sinus nodal tissues of rabbits and superfused guinea-pig ventricular muscles. In rabbit hearts, KW-3049 at concentrations above 10(-7) M caused a dose-related prolongation of atrio-His bundle conduction time (AH), whereas His bundle-ventricular conduction time (HV) was unaffected. In spontaneously firing rabbit sinus nodal tissues, KW-3049 at concentrations above 10(-8) M prolonged cycle length significantly. At 10(-6) M, amplitude and the maximum upstroke velocity of sinus nodal action potential were decreased as well. In normally polarized guinea-pig ventricular muscles under 4 mM [K+]0, KW-3049 at concentrations above 10(-6) M shortened the action potential duration without affecting the resting membrane potential and the maximum upstroke velocity of action potential (Vmax). The Vmax of slow action potentials induced by isoproterenol at 10(-7) M was inhibited significantly by additional application of KW-3049 at concentrations above 10(-9) M. At above 10(-8) M, the amplitude and duration of slow action potentials were reduced significantly. The potency of this slow action potential inhibition by KW-3049 was slightly less than that of nifedipine, while it was 10 to 100 times greater than that of verapamil. Spontaneous activity of ventricular muscles induced by BaCl2 at 1 mM was abolished completely at 16 min after application of KW-3049 at 10(-7) M. These results suggest that KW-3049 may have a potent and selective inhibitory action on cardiac slow calcium channels.

Animals↗
PubMed1986

Open and inactivated sodium channel block by class-I antiarrhythmic drugs.

Inhibitory action of six Class-I antiarrhythmic drugs on cardiac sodium channel was examined in isolated guinea-pig ventricular muscles. Transmembrane potential of the tissue was controlled by single sucrose gap voltage clamp technique. Following 30 sec quiescent period, a conditioning clamp pulse was applied from resting potential level to 0 mV for 10 msec to 800 msec. 100 msec after returning to the resting potential, voltage clamp was released and an action potential was elicited to measure its maximum upstroke velosity (Vmax) as an index of sodium channel availability. Under control condition such clamp pulse application did not affect the value of Vmax. In preparations treated with quinidine, and disopyramide, Vmax was decreased appreciably by the shortest clamp pulse application, but the Vmax reduction was enhanced only slightly by prolongation of the clamp pulse duration. In cases with lidocaine, mexiletine, tocanide and aprindine, the decrease in Vmax was enhanced much more remarkably by similar prolongation of the clamp pulse duration. These findings suggest the quinidine and disopyramide may block sodium channel mainly during open state. In contrast, lidocaine, mexiletine, tocainide and aprindine may block the channel mainly during inactivated state. Such a difference would cause wide variety of action potential duration dependency for the effects of Class-I drugs.

Action Potentials↗
PubMed1985

Anisotropic conduction properties of canine ventricular muscles. Influence of high extracellular K+ concentration and stimulation frequency.

The effects of fiber direction on the conduction of excitation and the characteristics of both extracellular and intracellular action potentials were examined in isolated dog ventricular muscle preparations. Conduction velocity and amplitude of extracellular potentials during propagation in the direction parallel to the long axis of fibers (longitudinal propagation) were significantly greater than those during propagation in the direction perpendicular to it (transverse propagation). However, the maximum rate of rise and amplitude of intracellular action potential were significantly greater during transverse propagation than during longitudinal propagation. Compared with the transverse propagation, the longitudinal propagation was more susceptible to conduction failure under high extracellular K+ concentration, suggesting a lower safety factor of the latter mode of propagation in depolarized cardiac tissue. In contrast, high frequency stimulation caused a greater decrease in the conduction velocity during transverse than longitudinal propagation resulting in augmentation of anisotropic conduction properties. These results suggest that the anisotropic conduction properties of cardiac tissue may play important roles in conduction disturbances leading to arrhythmias under various pathological conditions.

Action Potentials↗
PubMed1985

N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent: effects on cardiac conduction.

Effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165) on cardiac conduction were studied in anesthetized, anesthetized open-chest and conscious dogs and rabbit Langendorff hearts following either intravenous (i.v.) bolus injection and continuous infusion or intraarterial injection. SUN 1165 at antiarrhythmic doses (or concentrations), prolonged PQ interval in dogs inherently showing broad QRS complex without affecting QRS duration, but prolonged both PQ interval and QRS duration in dogs showing narrow QRS complex, in a dose-dependent manner. At higher doses (or plasma concentrations), SUN 1165 caused a marked prolongation of PQ interval together with QRS duration and subsequently, in most cases, elicited conduction block within the atrial muscle as evidenced by disappearance of P wave. SUN 1165 caused the dose-related prolongations of atrio-ventricular conduction time and intra-atrial conduction time, and at the highest dose it blocked conduction within the atrial muscle in some cases. In the rabbit Langendorff hearts, SUN 1165 tended to prolong intraatrial and His-Purkinje-ventricular conduction time in preference to atrio-ventricular one. At higher concentrations, SUN 1165 produced conduction block in the Purkinje-ventricular system. These results suggest that SUN 1165, at the antiarrhythmic doses (or plasma concentrations), causes a delay of cardiac conduction by acting on the atrial muscle and His-Purkinje-ventricular system without affecting conduction through A-V node region, and at higher doses (or concentrations) produces conduction block by acting again on the atrial muscle or on His-Purkinje-ventricular system without impairing conduction in the A-V node.

Animals↗
PubMed1984

Body surface isopotential maps in old anterior myocardial infarction undetectable by 12-lead electrocardiograms.

Body surface isopotential maps were recorded in 30 normal subjects and 32 patients with clinical evidence of old anterior myocardial infarction but without ECG findings of infarction. Position of the minimum in maps was compared at 5 msec intervals from the onset of QRS between the normal and infarction groups. A significant difference in the mean position of the minimum was observed at 5, 10, 15, 20, and 25 msec (p less than 0.001). The minima for the two groups achieved their clearest separation at 15 msec. Twenty-six of the 32 infarction patients showed the minima on the anterior chest, but 29 of the 30 normal subjects showed the minima on the back. These findings suggest the highly specific usefulness of body surface maps for the diagnosis of the presence of old anterior infarction undetectable by 12-lead ECGs.

Adult↗
PubMed1984

Body surface isopotential maps in old inferior myocardial infarction undetectable by 12 lead electrocardiogram.

The purpose of this study is to examine the value of body surface isopotential maps in the diagnosis of old inferior myocardial infarction that can not be diagnosed by 12 lead ECG. Forty-three patients with a Q wave of at least 0.02 sec but less than 0.04 sec in width and also less than 25% of the R wave in depth in lead a VF of the 12 lead ECG were selected for this study. The patients were divided into infarction and noninfarction groups based on their clinical histories and cardiac catheterization data. The infarction group showed characteristic surface maps with a minimum which moved from the left posterior chest to the lower back or from the lower back to the right anterior lower chest in the early phase of QRS. The noninfarction group exhibited a minimum which shifted from the back to the right upper chest or from the left anterior chest to the lower back in the same phase. Thus, both groups were clearly distinguishable from each other by the positional change of the minimum in the early phase of QRS. This study suggested that body surface maps contain diagnostic information concerning the presence or absence of inferior myocardial infarction which is not easily available from the 12 lead ECG.

Adult↗
PubMed1984

Electromechanical effects of bepridil on rabbit isolated hearts.

Electromechanical effects of a new antianginal agent, bepridil, on Langendorff-perfused rabbit hearts were compared with those of verapamil and lidocaine. Bepridil at concentrations above 2 X 10(-7)M caused a dose-related decrease in heart rate (HR), a prolongation of the atrio-His bundle conduction time (A-H interval) and a prolongation of the functional refractory period (FRP) of the atrioventricular (A-V) node. Similar changes in HR, A-H interval and the FRP of the A-V node were observed with verapamil at concentrations above 2 X 10(-8)M. Lidocaine at above 4 X 10(-5)M prolonged slightly the A-H interval and the FRP of the A-V node but did not decrease the HR. Bepridil at concentrations above 10(-6)M prolonged both the His bundle-ventricular conduction time (H-V interval) and the effective refractory period (ERP) of ventricular muscles. Similar changes in the H-V interval and in the ERP of ventricular muscles were observed with lidocaine at above 10(-5)M. Verapamil ranging between 5 X 10(-8)M and 8 X 10(-7)M had no effect on the H-V interval and appreciably shortened the ERP of ventricular muscles. Bepridil at concentrations above 2 X 10(-6)M reduced the developed tension as did verapamil at above 10(-7)M. On a molar basis, the depressant effect of bepridil on HR and the A-V nodal conduction, which may reflect inhibitory action on the slow channels, was less than one tenth that of verapamil. Bepridil was more potent than lidocaine in prolonging the H-V interval and the ERP of ventricular muscles indicating a possible inhibition of the fast sodium channels. Both of these electrophysiological effects of bepridil may afford significant bases for the antiarrhythmic action of the drug.

Animals↗
PubMed1984

Effects of bepridil on the electrophysiological properties of guinea-pig ventricular muscles.

Effects of bepridil, a new antianginal and potential antiarrhythmic agent, on transmembrane action potentials of ventricular muscles were examined in isolated right ventricular papillary muscles of guinea-pig. Bepridil at concentrations above 5 X 10(-6)M caused a dose-dependent decrease in both the maximum upstroke velocity (Vmax) and the action potential duration from the upstroke to 30% repolarization ( APD30 ). On the other hand, the resting potential (RP), the amplitude of action potential (AMP), and the action potential duration from the upstroke to 90% repolarization ( APD90 ) were not affected even at the highest concentration applied (10(-5)M). The curves relating membrane potential and Vmax were shifted by bepridil at 5 X 10(-6)M along the voltage axis in the direction of more negative potentials. The recovery kinetics of Vmax assessed by premature stimuli were definitely slowed by bepridil at above 10(-6)M. This effect was more pronounced with higher [K+]o (10 mM) than normal [K+]o (5 mM). Bepridil at 5 X 10(-6)M caused a rate-dependent decrease of Vmax (use-dependent block) with rapid onset and offset, as did lidocaine. Slow responses, which had been induced by isoprenaline (5 X 10(-6)M) in K+-depolarized preparations, were suppressed significantly by additional application of bepridil at 10(-5)M. These findings suggest that bepridil has electrophysiological characteristics similar to those both of Class Ib and Class IV antiarrhythmic drugs.

Action Potentials↗