Search PubMed⌕ Search

Biomedical subjects

T Saikawa

Publications and source records attributed to T Saikawa.

11 recordsLinked to original sources
PubMed1992

Mexiletine and disopyramide suppress ventricular premature contractions (VPC) irrespective of the relationship between the VPC and the underlying heart rate.

The effects of mexiletine (300 mg/day, 24 patients) and disopyramide (300 mg/day, 20 patients) on ventricular premature contractions (VPCs) were studied using a 24-hour ambulatory electrocardiogram. The VPC frequency was evaluated as a function of the underlying heart rate (HR). The VPC-HR correlation was classified into 2 major types, depending on whether the frequency of the VPC increased with the increased HR (positive type) or not (nonpositive type). The effects of the drugs were assessed based on the VPC-HR correlation and on the percent reduction of the VPC frequency. Mexiletine and disopyramide significantly decreased the frequency of the VPCs of both the positive and nonpositive types. Each drug was assumed to be effective when the percent reduction of the VPC frequency exceeded 70%. Mexiletine (300 mg/day) was 58.5% effective in positive type patients and 33.3% effective in nonpositive type patients, with a total efficacy of 45.8%. Disopyramide was effective in 50% of total cases with 44.4% in positive type patients and 54.5% in nonpositive type patients. However, the efficacy of these drugs on the 2 different types of VPCs was the same statistically. The findings strikingly contrasted those obtained with diltiazem and atenolol, which predominantly suppressed VPCs of the positive type which share similar characteristics with a triggered activity in vitro. We conclude that the mode of action of class I antiarrhythmics on the VPCs differs from that of class II or IV antiarrhythmics, as viewed from the VPC-HR relationship, and that the difference probably comes from the different arrhythmogenesis for positive and nonpositive types of VPCs, in addition to the different electrophysiological actions of mexiletine and disopyramide.

Cardiac Complexes, Premature↗
PubMed1979

Electrophysiological actions of mexiletine (Kö1173) on canine Purkinje fibres and ventricular muscle.

1 The effects of mexiletine (Kö1173) were investigated in canine isolated cardiac Purkinje fibres and ventricular muscle with microelectrodes. Some Purkinje fibres were depolarized by mechanical stretch to induce spontaneous activity with slow upstroke velocity. The preparations were stimulated at rates of 1, 2, 3 and 4 Hz. The drug concentrations tested were 0.4, 2 and 10 mug/ml in Tyrode solution (KCl = 5.4 mM).2 The ;therapeutic' drug concentration (2 mug/ml) shortened action potential duration and effective refractory period of Purkinje fibres, the effect being pronounced at lower stimulation rates. In ventricular fibres, action potential duration changes were not consistent while the effective refractory period was prolonged.3 In depolarized Purkinje fibres showing automatic activity, the drug (0.4 or 2 mug/ml) depressed phase 4 depolarization and reduced the firing rate without changing maximum diastolic potential. However, when depolarized Purkinje fibres were electrically driven at a constant rate, the maximum diastolic potential became more negative with a concomitant decrease of pacemaker slope and increase of maximum rate of rise (V(max)) of action potentials.4 Moderate (2 mug/ml) to high (10 mug/ml) concentrations of the drug depressed V(max) in Purkinje fibres stimulated at 2 Hz by 12 and 42% respectively and depressed ;membrane responsiveness'. The decrease in V(max) depended upon the stimulation rate, being minimum at the lowest (1 Hz) and maximum at the highest (4 Hz) stimulation rate.5 The drug (2 mug/ml) improved V(max) of the earliest propagated premature action potentials by shifting the takeoff potential to more negative levels in both Purkinje and ventricular fibres.6 Membrane conductance in fibres mounted in a single sucrose gap chamber was increased by the drug (2 mug/ml) in both fibre types in normal and in Na(+)-deficient solutions. This increase was attributed to an increase in membrane K(+) permeability produced by the drug.7 All these effects are similar to those of lignocaine, diphenylhydantoin or aprindine, and can explain the antiarrhythmic action of mexiletine.

Animals↗
PubMed1977

Electrophysiologic effects of diltiazem, a new slow channel inhibitor, on canine cardiac fibers.

The effect of diltiazem hydrochloride (CRD-401), a coronary vasodilator, was investigated in isolated perfused canine ventricular muscles and Purkinje fibers using microelectrodes. The drug at a concentration of 1 microng/ml lowered the level of action potential plateau and shortened the duration in both ventricular and Purkinje fibers without change in maximum rate of rise (Vmax) or resting potential. Contractile tension of ventricular muscle was markedly decreased with shortening of plateau. With higher drug concentrations (5 microng/ml), Vmax in both ventricular muscle and Purkinje fiber decreased about 20% without change in resting potential, and the effect on repolarization became more marked. The drug blocked spontaneous firing which appeared in depolarized Purkinje fibers and abolished the automaticity elicited in electrically depolarized ventricular muscles. Input resistance of ventricular muscle, measured by small, hyperpolarizing short pulses, was not changed appreciably by the drug; suggesting no change in potassium conductance. These results suggest that the drug is a slow channel inhibitor, and its clinical implication is discussed in terms of antiarrhythmic activity.

Action Potentials↗
PubMed1976

Automaticity and time-dependent conduction disturbance produced in canine ventricular myocardium. New aspects for initiation of ventricular arrhythmias.

1) In isolated canine ventricular myocardium, automaticity could be induced by a passage of small depolarizing DC-currents. The mechanism was attributed to inflowing Ca++ and Na+ currents and time-dependent deactivation of outward K+ current under a condition of high membrane resistance due to an anomalous rectification. Significance of the automaticity was discussed in relation to the ventricular arrhythmias encountered in very early stage of myocardial infarction. 2) In in situ canine hearts, chloropromazine induced time (preceding cycle length)-dependent decrease in conduction velocity within the ventricle. Thus QRS-duration of non-premature beats was lenghtened at rapid pacing rates while QRS-duration of atrial premature beats was lengthened also at short coupling intervals in the drug-treated dogs. These slow conductions were not due to reduced take-off potential of action potentials bue due to drug-induced slow recovery of rapid Na+ system. The phenomenon may be responsible for reported QRS-prolongation and fatal ventricular arrhythmias encountered in the patients receiving phenothiazines.

Action Potentials↗
PubMed1976

Spontaneous electrical activity induced by depolarizing currents in canine ventricular myocardium. A preliminary note.

Spontaneous action potential (AP) discharge could be induced by an application of long (5-10 sec) depolarizing currents in 68% of canine ventricular myocardium tested in the voltage range between about -65 and -10 mV. The constant currents of various intensities were applied across a sucrose gap, and intracellular potentials were recorded with a microelectrode. The firing rate of the AP's was voltage-dependent and ranged between 0.7 and 2.5 Hz. The AP was dependent on both [Ca++]0 and [Na+]0. Increase of [Na+]0. Increase of [Na+]0 from 37 to 149 mM increased the firing rate, maximum rate of rise, and overshoot of the AP's while increase of [Ca++]0 from 0.45 mM to 1.8 and 7.2 mM increased the firing rate and maximum rate of rise, but did not change the amplitude of overshoot. AP discharges were not blocked by tetrodotoxin (10(-5) Gm/ml), but were effectively blocked by verapamil (6 X 10(-6) Gm/ml). Adrenaline (5 X 10(-6) Gm/ml) initiated AP's in otherwise quiescent preparations. The results suggest that spontaneous AP's may be produced by inflowing of slow Na+ and Ca++ currents modified by underlying change of K+-permeability. Possible clinical significance of this phenomenon is discussed in relation to ventricular arrhythmia.

Action Potentials↗
PubMed1976

The prolongation of QRS-duration resulting from delayed recovery of ventricular excitability. A new mechanism for intraventricular conduction disturbance. A preliminary note.

Chlorpromazine (1, 5, and 20 mg/Kg) was injected intravenously to anesthetized and open-chest dogs under artificial respiration. Using right atrial pacing, the heart rate was increased stepwise from intrinsic sinus rate to higher rate where the A-V block first developed. ECG (II) was recorded simultaneously with arterial blood pressure, ventricular monophasic action potentials and left atrial electrogram. In the control, QRS-duration was constant (46.9 +/- 0.8 msec) irrespective of heart rate. After the drug injection, however, the duration increased significantly with increasing heart rate, the effect depending on the injected dosage (r==0.283, P less than 0.1 in 1 mg/Kg; r==0.406, P less than 0.01 in t mg/Kg; r==0.631, P less than 0.001 in 20 mg/Kg). During the drug action, QRS-duration of atrial premature beats was also longer than that of sinus beats, and the lengthening increased with shortening of preceding cycle length. The observed QRS-prolongations were due to neither incomplete ventricular repolarization nor bundle branch block. The mechanism of prolongation was attributed to delayed or time-dependent recovery of ventricular excitability, i.e., slowed removal of inactivation in rapid sodium system in the ventricular muscle fibers.

Animals↗
PubMedDate not supplied

Electrically induced automaticity in canine ventricular myocardium.

Repetitive spontaneous action potentials (SAP) could be induced in canine ventricular and atrial muscle, although this inhibitory action was antagonized by the pretreatment with voltage range between about -60 mV and 0 mV. The SAP seemed dependent on both slow inward Ca2+ and Na+ currents and was suppressed by verapamil, Mn2+, and diltiazem, but not by tetrodotoxin. The increase of extracellular potassium concentration also suppressed the SAP. Acetylcholine could not block the SAP in ventricular muscle, but inhibited that in atrial muscle, although this inhibitory action was antagonized by the pretreatment with atropine. The automatic activity was attributed to slow inward Ca2+ and Na+ currents modified by decreasing time-dependent K+ outward current and K+ anomalous rectification.

Action Potentials↗
PubMedDate not supplied

Intraventricular conduction disturbance due to delayed recovery from ventricular inactivation in chlorpromazine-treated dogs.

In in situ canine hearts, chlorpromazine induced a time (preceding cycle length)-dependent decrease in conduction velocity within the ventricle. Thus, QRS duration of nonpremature beats was lengthened at rapid pacing rates while QRS duration of atrial premature beats was lengthened at short coupling intervals. These slow conductions were not due to reduced take-off potential of ventricular action potentials but to drug-induced slow recovery of the rapid Na+ system. The phenomenon may be responsible for reported QRS prolongation and fatal ventricular arrhythmias encountered in patients receiving phenothiazines.

Action Potentials↗