[Electrophysiological effects of bunaftine, an antiarrhythmic drug, on action potential characteristics in ventricular muscle preparations].

The electrophysiological effects of bunaftine were studied using the glass microelectrode technique. Bunaftine at 1, 5 and 10 mg/l produced a concentration-dependent depression of the maximum rate of rise of the action potential in guinea pig papillary muscle preparations without affecting the resting membrane potential and the action potential amplitude. The action potential duration (APD50, APD90) was significantly prolonged by the treatment with 1 and 5 mg/l bunaftine, while it was not changed by the treatment with 10 mg/l. The absolute refractory period (ARP) was also prolonged dose-dependently by the treatment of bunaftine; It was excessively prolonged (177% of control) at the concentration of 10 mg/l. Disopyramide produced similar electrophysiological changes to those of bunaftine except for the prolongation of ARP. ARP/APD90 ratio was significantly increased by bunaftine, but not by disopyramide. These electrophysiological effects of bunaftine and disopyramide observed in guinea pig ventricular preparations were similarly found in canine ventricular muscle preparations. These results indicate that the electrophysiological characteristics of bunaftine are similar to those of disopyramide in that the most prominent effect was the prolongation of ARP.

Effects of bunaftine on morphology, microfilament integrity, and mitotic activity in cultured human fibroblasts and HeLa cells.

Human fibroblasts and HeLa cells were treated with bunaftine (N-butyl-N-/2-(diethylamino)ethyl/-1-naphthalenecarboxamide ) in vitro. At concentrations of 0.5-2.0 mM, the drug caused contraction and rounding of the cells with loss of microvilli-like processes. Aggregates of dense, partly granular, partly fibrillar material formed in the cytoplasm and the rough endoplasmic reticulum became vesiculated. Immunofluorescence microscopy with DNase I and anti-DNase I demonstrated that bundles of actin filaments were disrupted, forming rings, coils, and granules. Filaments stained with antibodies to vimentin (fibroblasts) and prekeratin (HeLa cells) showed less characteristic rearrangements, probably related to the rounding up of the cells. 0.4 mM bunaftine increased and 0.8-1.0 mM markedly decreased the percentage of mitotic cells, without accumulation of cells in any particular stage of mitosis. The drug may arrest the cell cycle at some point before mitosis; it may have a critical concentration above which the arrest becomes permanent. These results suggest that bunaftine interferes with the integrity of microfilament bundles in a different manner from that of cytochalasins. It does not cause any depletion of cellular ATP, indicating that its effect is not a result of inhibition of cell metabolism. It is proposed that bunaftine may be used a complement to cytochalasins in studies of the microfilament system of the cell. The possible binding of bunaftine to actin or myosin and further details of its mechanism of action remain to be elucidated.

Effects of bunaphtine on 45Ca movements in rat aortic smooth muscle.

The effect of bunaphtine (BNA, 5 X 10(-5)M) on La3+ -resistant 45Ca content and 45Ca efflux was studied on rat aortic smooth muscle. BNA decreased both control and norepinephrine-stimulated La3+-resistant 45Ca content and increased the 45Ca efflux. These effects could explain the inhibition of the contractile responses induced by BNA.

Intropic effects of several antiarrhythmic drugs.

The effects of intravenous administration of several quinidine-like antiarrhythmic drugs (bunaftine, monochloroacetyl ajmaline, lidocaine, mexiletine, disopyramide, aprindine, diphenylhydantoin, procainamide) on left ventricular performance, evaluated by systolic time intervals (STI), were studied in 100 patients with atherosclerotic heart disease. The STI were measured: the pre-ejection period (PEP), the isometric contraction time (ICT), the left ventricular ejection time (LVET), corrected LVET (LVETc), and the PEP/LVET ratio. The degree of impairment of left ventricular performance was maximal after aprindine and disopyramide administration. This was demonstrated by significant increases in the PEP, ICT, and PEP/LVET and by significant decreases in LVET and LVETc, in patients in both III-IV and I-II NYHA classes. Bunaftine, monochloroacetyl ajmaline, and lidocaine induced a less marked impairment of myocardial performance, since the PEP, ICT, and PEP/LVET increases were not significant compared to controls in patients in NYHA class I-II, and since no variation of LVET and LVETc were observed. Mexiletine effects on myocardial performance appear to be intermediate between these groups of drugs. Diphenylhydantoin and procainamide, considered separately because of their effects on heart rate and blood pressure which are not possessed by the other drugs, induced significant increases of PEP in NYHA class III-IV patients. However, the effects of these 2 drugs on myocardial performance may have been underestimated, due to the concomitant hemodynamic effect of these drugs.

[Mobile coronary unit of Florence: early care of arrhythmias not due to acute coronary insufficiency]. / Unità coronarica mobile di Firenze: intervento precoce per disturbi del ritmo non dipendenti da insufficienza coronarica acuta.

The aim of Mobile Coronary Care Units (M.C.C.U.) is to reduce the delay in delivering intensive care to patients with a heart attack. In the city of Florence a M.C.C.U. has been available since November 1979. During the first year the staff of the M.C.C.U. has treated 158 cases of serious cardiac arrhythmias which occurred among 486 interventions. In 94 patients cardiac arrhythmias followed an acute coronary attack. In 64 patients coronary heart disease could not be demonstrated. This study concerns the latter group of patients. The mean age was 65.2 years and 39 patients (61%) were women. The mean time from the onset of the symptoms to the arrival of the M.C.C.U. team was 3h and 2 min, whereas the mean time from the call to the arrival was 14 min. Sixty patients had atrial arrhythmias (29 atrial fibrillation, 2 atrial flutter, 22 atrial tachycardia, 7 premature atrial contractions) and 4 patients had ventricular arrhythmias (1 ventricular tachycardia, 1 ventricular flutter, 2 premature ventricular contractions). In thirty-nine patients (61%) the cardiac arrhythmia was abolished by the staff of the M.C.C.U.. Of the remaining 28 patients, 10 were brought to the hospital and 18 were left at home. None of these needed later admission to the hospital. So the treatment at home of cardiac arrhythmias has been successful in the majority of patients. Bunaftine was the antiarrhythmic drug more frequently used (23 cases, 34%) with a high percentage of success (87%). In planning medical emergency services to the community, one can envisage the use of the M.C.C.U. facilities to treat at home those arrhythmias that are not associated with an acute coronary attack.

[Pharmacological therapy and prevention of recurrent ventricular tachycardia]. / Terapia e prevenzione farmacologica delle tachicardie ventricolari ricorrenti.

Treatment of recurrent ventricular tachycardia (RVT) is still difficult, as far as choice of antiarrhythmic agents, dosage, associations and statement of their effectiveness are concerned; the Authors report their experience on twelve cases of RVT. The diagnosis of ventricular tachycardia was confirmed by esophageal electrograms in four cases and by intracardiac recordings in two cases. Patients were controlled by clinical observation, continuous electrocardiographic monitoring and several recordings. Ambulatory electrocardiographic monitoring was carried out in ten patients. Two patients left the hospital spontaneously; therapy was found to be effective in the remainder. Four patients were treated with quinidine plus betablockers, for cases with quinidine plus amiodarone. The results of long-term follow-up suggest that combined pharmacological therapy with drugs of different classes may be successful in preventing recurrences of ventricular tachycardia. The Authors think that careful choices of adequate therapeutic programs and rigid criteria for the evaluation of results should be planned in apparent refractory RVT, before referring to invasive procedures.

Electrophysiological effects of bunaphtine in guinea-pig ventricular fibers.

The electrophysiological effects of bunaphtine (BNA) in concentrations between 10(-7) M and 10(-4) M were studied on action potential characteristics of guinea-pig ventricular fibers. In fibers stimulated at constant rate, BNA, greater or equal to 10(-5) M, did not change the resting membrane potential but significantly decreased the amplitude and maximum rate of rise of the action potential and shifted the membrane responsiveness and membrane reactivation curves downward and to the right. At concentrations greater than or equal to 10(-6) M both action potential duration and effective refractory period were prolonged. BNA also decreased ventricular excitability and maximum following frequency and suppressed the pacemaker activity induced in ventricular muscle fibers by Ba ions or by adrenaline. However, it did not modify the Ca-mediated action potentials. The mechanism responsible for the in vivo antiarrhythmic action and side effects are discussed.

Electrophysiological effects of bunaphtine on isolated rat atria.

The effects of a new antiarrhythmic, bunaphtine, on the electrical and mechanical activity of isolated rat atria were compared with those of quinidine and amiodarone. Both electrically stimulated and spontaneously beating atria were used. In spontaneously beating double atria bunaphtine produced a dose-dependent decrease in the rate, contractile force, work index and maximum following frequency at which the atria could respond to electrical stimulation, depressed the pacemaker activity and increased the sinus node recovery time. In isolated left atria bunaphtine prolonged the effective refractory period and decreased atrial excitability. Bunaphtine did not block positive chronotropic and inotropic responses to isoprenaline and did not reduce the positive inotropic effect of raised calcium concentrations. These results support the hypothesis that bunaphtine exerted on isolated atria a direct cardiodepressant effect similar to that of quinidine, and that it may be classified as a class 1 antiarrhythmic according to the classification of Vaughan Williams.

[Supraventricular tachyarrhythmias. Therapeutical efficiency of bunaftine administed in rapid bolus (author's transl)]. / Tachiaritmie sopraventricolari. Efficacia terapeutica della bunaftine somministrata in bolo rapido.

The authors exhibit the results obtained in 25 patients sumministring bunaftine in 3 mg/Kg in 1-2 min in rapid bolus i.v. By means a continuous ECG registration they could state that the antiarrhythmic effect is simultaneous with the distribution of the drug, obtaining the restoration of the sinus rhythm in about 90% of the patients. The Authors remark the lack of meaningful collateral effect by means a pre-treatment with diazepam-cortisone, according to their method.

[Interaction of an anti-arrhythmic drug (bunaftine) with cardiac myosin]. / Interazione di un antiaritmico (bunaftine) con miosina cardiaca.

The interaction of Bunaphtine with cardiac myosin has been investigated by means the method of differential spectra. The results demonstrate the existence of a qualitative variation of the spectrum, which indicates an effective interaction drug-protein.

Interaction of cocaine and bunaphtide on the 3H-norepinephrine uptake mechanism on isolated left atrium of guinea-pig.

Bunaphtide induces a blockade in the 3H-norepinephrine uptake and retention in the isolated guinea-pig left atrium. However, this blockade does not seem to be related with the cardiodepressant effect of the drug.