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At least 55 records · Page 3Linked to original sources
PubMed1987

Cholestasis and changes in the microcirculation of perfused rat liver caused by the calcium ionophore A23187 and type I antiarrhythmic drugs.

The calcium-ionophore A23187 causes a reversible increase of the hydrostatic pressure in the portal vein of perfused rat liver. Concomitantly, hepatic functions like the production of bile and the transhepatic movement of the bile acid taurocholate are diminished, mainly due to decreased uptake. These phenomena are partly explained by changes in the microcirculation of the liver, visualized by Trypan blue staining. Both the increase in portal pressure and the major part of the decrease of biliary excretion of taurocholate and bile flow are prevented by the addition of the vasodilator papaverine. The type I antiarrhythmic drugs quinidine and N-propylajmaline bitartrate (NPA), at high concentrations, also induce a rise in portal pressure and act as a cholestatic agent. The rise in portal pressure caused by NPA requires the presence of extracellular calcium and is counteracted by papaverine. In contrast to A23187, the cholestasis caused by NPA is not influenced by papaverine. While NPA decreases the hepatic uptake and biliary excretion of taurocholate, papavarine is able to restore only the uptake and not the excretion. The concentration of taurocholate in the bile is not significantly changed by NPA.

Animals↗
PubMed1989

Three types of atrioventricular reciprocating tachycardia using bilateral accessory pathways in a patient with Wolff-Parkinson-White syndrome.

Electrophysiologic studies were performed on a patient with Wolff-Parkinson-White syndrome and recurrent supraventricular tachycardia. Bilateral accessory pathways capable of antegrade and retrograde conduction and three different types of atrioventricular (AV) reciprocating tachycardia were demonstrated. One type of narrow QRS tachycardia used the normal AV pathway for antegrade conduction and the left-sided accessory pathway for retrograde conduction. Two types of wide QRS tachycardia (one with right bundle branch block and one with left bundle branch block) used both accessory pathways for antegrade and retrograde conduction, respectively, and were independent of the normal AV pathway. The data showed that bilateral accessory pathways have different electrophysiologic properties and participate in three different types of AV reciprocating tachycardia.

Administration, Oral↗
PubMed1991

Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes.

The effects of N-n-propylajmaline (prajmalium) on the Na and Ca currents of single frog atrial and ventricular cells were studied by means of the whole-cell patch-clamp technique. Prajmalium (10(-9) to 10(-6) M) depressed the Na current (INa) in a dose- and use-dependent manner. In the same range of concentrations, prajmalium induced a dual effect on the high (ICaL) and low (ICaT) threshold Ca currents (the latter being only present in atrial cells). At a low concentration (10(-9) M), prajmalium increased both Ca currents while at high concentrations (10(-6) M) it depressed them. Prajmalium appeared very potent on ICaT although this current is generally reported to be barely sensitive to agonists and drugs. The action of the drug was also accompanied by a shortening in the half-time of inactivation of the Ca currents and a slight hyperpolarizing shift of their availability curves. The increase in ICaL by prajmalium was not prevented by prazosin (10(-7) M) nor by propranolol (10(-6) M), and it was also observed after ICaL had been fully stimulated by isoproterenol (10(-7)M). Nifedipine (10(-6) M), however, was able to prevent or block the prajmalium-induced increase in ICaL. Some similarities between the actions of prajmalium and dihydropyridine agonists on Ca currents are discussed.

Animals↗
PubMed1991

Antiarrhythmic drugs impair hepatic uptake and secretory function by different mechanisms in the isolated perfused rat liver.

In the present study the effect of various antiarrhythmic drugs on hepatic perfusion parameters, uptake capacity of organic anions and biliary secretion using the isolated perfused rat liver was examined. Infusion of verapamil (VP), diltiazem, N-propyl-ajmaline (NPAB), and quinidine at pharmacological doses induced consistently a 1.4-1.6-fold increase in portal pressure accompanied by a approximately 60% decrease in bile flow and a approximately 65% inhibition of biliary taurocholate (TC) excretion. Furthermore, hepatic uptake of oxygen, bromosulphthalein (BSP), and TC was significantly reduced. All these effects were dose-dependent and reversible upon withdrawal of the drugs. Studies of the hepatic circulation using a Trypan blue staining technique demonstrated a patchy perfusion pattern during infusion of the antiarrhythmic drugs as compared to the homogenously stained control organ. The hemodynamic alterations and the impairment of the hepatic initial uptake function could be entirely prevented by concomitant administration of the vasodilator papaverine. Bile flow and biliary TC excretion, however, were still inhibited under these conditions. The present results indicate that antiarrhythmic drugs produce cholestasis in the isolated perfused rat liver independently of their adverse effect on hepatic hemodynamics.

Animals↗
PubMed1980

Cholestatic jaundice: an immune response to prajmalium bitartrate.

Cholestatic jaundice associated with chills, pruritus and blood eosinophilia developed in a patient who received prajmalium bitartrate therapy for ventricular arrhythmia following acute myocardial infarction. Discontinuation of the drug resulted in a spontaneous improvement in the clinical and biochemical findings. Challenge by prajmalium bitartrate caused rapid reappearance of the clinical and biochemical features. In immunological studies, deposits of IgG and IgA were detected at the bile canaliculi by fluorescent staining, and the patient's lymphocytes produced macrophage migration inhibition after in vitro incubation with prajmalium bitartrate. Thus, laboratory results support the assumption of an allergic mechanism.

Ajmaline↗
PubMed1989

On the mechanism of drug-induced blockade of Na+ currents: interaction of antiarrhythmic compounds with DPI-modified single cardiac Na+ channels.

In patch-clamped membranes from neonatal rat cardiocytes, elementary Na+ currents were recorded at 19 degrees C for study of the inhibitory influence of several antiarrhythmic drugs including lidocaine, diprafenone, propafenone, and prajmalium on DPI-modified cardiac Na+ channels. Diprafenone (20 mumol/l) and lidocaine (300 mumol/l) induced a voltage- and time-dependent block of reconstructed macroscopic sodium current (INa). The drugs depressed the sustained, noninactivating INa component (which reflects the number and open probability of DPI-modified Na+ channels) effectively, in a voltage- and time-dependent fashion. Once opened, DPI-modified Na+ channels are highly drug-sensitive. Antiarrhythmic drugs (propafenone, diprafenone, and, to a lesser extent, lidocaine) provoke a flicker block, that is, the long-lasting openings are chopped into a large number of short and grouped openings. This indicates rapid transitions between a drug-associated, blocked state and a drug-free, conducting state. The latter has a unitary conductance of 12 pS, very similar to the control value in the absence of antiarrhythmic drugs. The decrease in open time of drug-treated DPI-modified Na+ channels is concentration-dependent. Hill coefficients for propafenone of about 1.0 and for prajmalium of about 0.7 were calculated. A blocking rate constant of 6.1 x 10(7) mol-1sec-1 for propafenone, but of 1.5 x 10(7) mol-1sec-1 for prajmalium was obtained at -30 mV. The unblocking rate constant for propafenone was, also at -30 mV, about twice as large as the unblocking rate constant for prajmalium. The open channel block kinetics are essentially voltage-dependent. The affinity of the channel-associated drug receptor increases on membrane depolarization. The blocking rate constant was inversely related to the number of Na+ ions moving through the open channel. It is concluded that the manifestation of this voltage- and Na+-dependent flicker block is intimately related to removal of fast Na+ inactivation.

Animals↗
PubMed1982

Atypical ventricular tachycardia (torsade de pointes) induced by amiodarone: arrhythmia previously induced by quinidine and disopyramide.

A 44-year-old woman is described in whom amiodarone, disopyramide, and quinidine, administered alone separately, induced atypical ventricular tachycardia (AVT, torsade de pointes). Following a closed mitral valvotomy, she received quinidine, 1.2 g/day, without interruption for 17 years. Because of a recurrence of paroxysmal atrial fibrillation, the dose of the drug was increased to 1.4 g/day; 24 hours later AVT with syncope developed but responded promptly to atropine. Two years later, 24 hours following an increase in the dose of disopyramide from 300 to 600 mg/day, AVT with syncope occurred; isoproterenol abolished the arrhythmia instantly. Amiodarone was the third drug to induce AVT in this patient; she received 200 mg/day six days per week for six months. The dose was subsequently increased to 200 and 400 mg/day on alternate days, six days per week, and two months later AVT occurred. That time the only effective treatment was ventricular pacing.

Adult↗
PubMed1992

[Anti-arrhythmic effectiveness of neogilurhythmal in extrasystolic arrhythmia].

The paper provides the results of differential neogilurythmal therapy in 20 patients with high-grade atrial and ventricular premature contractions in the presence of coronary heart disease. The detection of cardiac arrhythmias and evaluation of the antiarrhythmic efficacy of neogilurythmal were performed by Holter monitoring and transesophageal electrophysiological study. After the baseline studies, the antiarrhythmic efficacy of the drug was evaluated during an acute drug test and then during a 8-day course of the therapy. In the acute drug test, the dose of neogilurythmal was 50% of the daily dosage. The studies indicated that neogilurythmal in a dose of 80 mg/day was beneficial in affecting both the atrial and ventricular extrasystolic arrhythmia. The agent failed to alter heart rate, sinus nodal function and atrioventricular conduction. Thus, neogilurythmal is low toxic and produces no adverse effects when given in the definite dosage range.

Adult↗
PubMed1992

Prajmalium, an antiarrhythmic with positive inotropic effect: mechanism of action in rabbit single cardiomyocytes.

The propyl derivative of ajmaline, N-n-propylajamaline (prajmalium), is an antiarrhythmic compound that lacks the commonly reported negative inotropic effects of all others under clinical use. The present study was undertaken to establish and understand its effects at the cellular level in mammalian preparations. Electrical and mechanical activities were recorded from right ventricular strips and Na and L-type Ca currents (INa and ICaL, respectively) were recorded with the whole-cell patch-clamp technique in right ventricular myocytes freshly dissociated from rabbit hearts. Prajmalium decreased the maximal rate of depolarization of the action potential in a dose-dependent manner with an EC50 of 3 microM. This effect was use and frequency dependent. Action potential duration was increased by 1 microM prajamalium but decreased on applying higher concentrations. The force of contraction was slightly (15%) increased at 0.1 microM, not affected at all at 1 microM and depressed by 30% at 20 microM. In single cardiomyocytes maintained at negative holding potentials, INa was slightly depressed by prajmalium at 10 nM and reduced by 75% at 10 microM. ICaL was increased by 30 and 20% on applying prajmalium at 1 and 10 microM, respectively; on the other hand, ICaL was reduced by these two concentrations of prajmalium at less negative holding potentials. A higher prajmalium concentration (100 microM) decreased ICaL at all holding potentials studies and this effect was enhanced with depolarization. The increase in ICaL induced by prajmalium (1 microM) was also observed after ICaL had been fully beta-adrenergic and P2-purinergic stimulated by isoproterenol (1 microM) in the presence of IBMX (100 microM) and ATP (10 microM). It is concluded that prajmalium is able to increase ICaL in rabbit ventricular cells in a voltage-dependent manner, an effect that could account in part for the observed lack of negative inotropism of this antiarrhythmic in clinics.

Action Potentials↗
PubMed1992

[Use-dependent inhibition of C-axon multimodal units of cat skin by lidocaine and N-propyl-ajmaline].

Subcutaneous application of local anesthetic drug lidocaine and cardiac antiarrhythmic n-propyl-ajmaline produced the reversible use-dependent inhibition of feline polymodal mechano-heat C-fiber cutaneous sensory units (CMH-units) excited by moderate noxious mechanical stimulus. The discharge rate as well as the number of evoked spikes of polymodal sensory units treated with the drugs decreased below the values observed under noxious chemical excitation of CMH-units. The repeated mechano-stimulation with 5 to 30 sec interval between stimuli produced complete though a reversible block of the treated units. Quaternary amine n-propyl-ajmaline induced use-dependent inhibition of CMH-units in lower concentrations than tertiary amine lidocaine. The use-dependent inhibition of CMH-units is discussed in connection with nociception and local analgesia.

Animals↗
PubMed2003

[Cholestatic hepatitis caused by prajmalium treatment: case report].

Prajmalium rarely causes idiosyncratic liver injury. Author describes the case of cholestatic hepatitis occurring in three weeks after cessation of short-term treatment with prajmalium. Eighteen months later, despite of good general status, physical and biochemical features of cholestasis were present. Pathologic examination of liver biopsy specimen revealed the chronic intracellular cholestasis with lymphocytic infiltration. Presented case indicate that even short-term treatment with potentially weekly hepatotoxic drug may cause the long-term intrahepatic cholestasis.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

[The anti-arrhythmia action of combinations of N-propylajmaline bromide with anti-arrhythmia agents of different classes].

In experiments on 68 dogs with ventricular arrhythmia at the late stage of experimental myocardial infarction caused by the coronary artery branch occlusion it was shown that combinations of N-propylaimaline bromide (IA class of antiarrhythmic agents) with trimecaine (IB class) or anapriline (II class) or phynoptine (IV class) induce a significant increase of the antiarrhythmic effect that is not observed at combination of N-propylaimaline with ethmosine (the both antiarrhythmic drugs belong to IA class). This potentiating effect is thought to be related to differences in the molecular mechanisms of action of antiarrhythmic drugs.

Ajmaline↗
PubMedDate not supplied

[The effect of a combination of N-propylajmaline bromide and trimecaine on heart arrhythmias of different origins and on the electrophysiological parameters of the myocardium].

In experiments on dogs and cats with disorders of the atrial and ventricular rhythms of various genesis the combination of N-propylaymalinebromide and trimecaine (the antiarrhythmic drugs of classes IA and IB) was found to potentiate the antiarrhythmic action. This effect was studied in electrophysiological experiments by using the microelectrode technique or on the dog and rat myocardium tissue. The combination of the antiarrhythmic drugs was shown to exert a more significant effect on some electrophysiological parameters determining the arrhythmic readiness of the myocardium.

Animals↗
PubMed1991

Pharmacokinetics and relative bioavailability of prajmalium bitartrate after single oral dosing.

Pharmacokinetics and relative bioavailability of the marketed prajmalium bitartrate tablet (Neo-Gilurytmal, CAS 2589-47-1) compared to an oral solution were investigated in an open, randomized, single-dose two-fold crossover study in 20 healthy male volunteers. One subject was identified to be a poor metabolizer. In the study population with normal metabolic status the two oral formulations proved to be bioequivalent with regard to the pharmacokinetic parameters Cmax, AUC(0-Tlast), AUC(0-infinity) and Ae(24h). tmax was prolonged after administration of the tablets. The relative bioavailability of prajmalium bitartrate from the tablet amounted to 112%. The poor metabolizer demonstrated in both oral formulations high plasma concentrations, increased AUCs and prolonged terminal half-lives as well as increased renal excretion of prajmalium bitartrate.

Adult↗
PubMed1991

[Combined action of anti-arrhythmia agents].

A significant potentiation of antiarrhythmic effect was observed in 121 dogs with arrhythmias 24 and 48 hours after the coronary artery ligation when the following drugs were combined: N-propylajmaline bromide (1A class) and trimecaine (1B class), quinidine (1A class) and trimecaine, N-propylajmaline bromide and anaprilin (2 class). The potentiation is attributed to the different molecular mechanisms of action of the drugs.

Animals↗