Effects Of Propafenone Research Articles

Meta-analysis confirms effectiveness of propafenone in SVT and AF

Meta-analysis confirms effectiveness of propafenone in SVT and AF

Placebo-controlled evaluations of propafenone for atrial tachyarrhythmias

This review summarizes the results of placebo-controlled trials of propafenone, a class IC antiarrhythmic drug, in patients with supraventricular tachycardia, atrial fibrillation (AF), and atrial flutter. Success rates for cardioversion from AF or flutter to sinus rhythm of 9–93% have been obtained with intravenous propafenone. The duration of arrhythmia is an important factor in the degree of success. The use of a single oral dose has also been reported to be effective in a number of studies. Several placebo-controlled studies have confirmed the effectiveness of propafenone in the long-term suppression of both supraventricular tachycardia and AF and flutter. These reported trials have shown consistent benefit with propafenone compared with placebo in preventing arrhythmia recurrence. The adverse side effect profile for propafenone has also been reviewed with particular reference to the potential for proarrhythmia. The rate of side effects is dose-dependent and tends to be higher in patients with underlying structural heart disease. Overall propafenone has been shown to be an effective antiarrhythmic drug with an acceptable side effect profile for the acute and long-term treatment of supraventricular arrhythmias.

Effects of pilsicainide and propafenone on vagally induced atrial fibrillation: role of suppressant effect in conductivity

The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in α-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)( n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)( n=10) was intravenously infused during stable atrial fibrillation sustaining >30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three ( p<0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group( p<0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone ( p<0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511–521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.

Postrepolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects.

Conduction block may be both antiarrhythmic and proarrhythmic. Drug-induced postrepolarization refractoriness (PRR) may prevent premature excitation and tachyarrhythmia induction. The effects of propafenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven different right and left ventricular sites, along with a volume-conducted ECG. All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate. MAPs were analyzed for action potential duration at 90% repolarization (APD90), conduction times (CT) between the pacing site and the other MAPs, and PRR (effective refractory period-APD90=PRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD90 by 12% and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing, whereas propafenone slowed mean CT by up to 400% (P<0.001 versus baseline and procainamide). Wavelength was not changed significantly by procainamide but was shortened fourfold by propafenone at S5. Both drugs produced PRR, which was associated with a 70% decrease in VF inducibility with procainamide and elimination of VF with propafenone. Despite this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. Drug-induced PRR protects against VF induction. Propafenone promotes slow monomorphic VT, probably by use-dependent conduction slowing and wavelength shortening.

Propafenone inhibition of human atrial myocyte repolarizing currents.

This study was aimed at defining cellular electropharmacologic effects of propafenone on repolarizing currents in human atrial myocytes. Whole-cell patch-clamp of enzymatically isolated atrial myocytes from 11 cardiac surgical patients aged between 29 days and 74 years revealed potent time- and concentration-dependent (IC50 = 4.8 +/- 0.4 mumol/l), but age-, voltage-, and frequency-independent propafenone inhibition of transient outward current. Time course of apparent transient outward current inactivation was best described by a single exponential process in the absence of propafenone and by a double exponential model in its presence, with drug-concentration-dependent acceleration of the fast exponential component. Neither voltage dependence of steady-state transient outward current inactivation nor time course of recovery from inactivation was affected by propafenone. Significant inhibition (P < 0.05) of the ultra-rapidly activating delayed rectifier and inwardly rectifying currents was observed only in the presence of > or = 10 mumol/l propafenone. These actions of propafenone could explain its repolarization prolonging effect and might contribute to clinical electrophysiologic responses which have been documented in patients of all ages.

Different Effects of Propafenone and Amiodarone on the Low Right Atrial Isthmus in Human Atrial Flutter: Insight Into the Mechanism of Termination

Different Effects of Propafenone and Amiodarone on the Low Right Atrial Isthmus in Human Atrial Flutter: Insight Into the Mechanism of Termination

Different effects of propafenone and amiodarone on the low right atrial isthmus in human atrial flutter: insight into the mechanism of termination

Different effects of propafenone and amiodarone on the low right atrial isthmus in human atrial flutter: insight into the mechanism of termination

Effects of Oral Propafenone in Patients with Frequent Ventricular Extrasystoles

Propafenone is an antiarrhythmic drug with class IC sodium channel blocking agent with mildly B-blocking and calcium channel blocking properties. Oral therapy effectively suppresses supraventricular and ventricular arrhythmias. However, experience with propafenone in Chinese patients is limited. To assess the efficacy and safety of oral propafenone in Chinese patients with frequent ventricular extrasys-toles(＞ 20/hour in average) and normal treadmill exercise test and echocardiographic results, 23patients (14 males and 9 females, mean age 56.5 years) were studied using 24-hour Holter ECG recording. Oral propafenone at a dose of 300 mg/day (12 patients) and 450 mg/day (11 patients) was then given. The 24-hour Holter ECG recording was repeated 4 weeks later to evaluate the suppressive effect of propafenone. Blood pressure and adverse effects were also recorded at each visit. When all patients taking 300 mg/day were analyzed as a group, no stastistically significant suppression of ventricular extrasystoles was noted, whereas patients taking 450 mg/day had significant suppression of total ventricular ectopies, isolated ventricular ectopies, and average ventricular ectopiees. Therapeutic success (＞85% suppression of ventricular ectop) was achieved in 41.7% (5/12) of in those taking 300 mg/day and in 63.6% (7/11) of those taking 450mg/day. Of the three patients taking 450 mg/day, who did not achieve ＞85% suppression, two patients showed significant suppression of ventricular ectopies without adverse effects when the dose was increased to 600 mg/day. During the treatment period, no patient reported arrhythmia-related ill effects or developed hemodynamic instability, although three patients had transient and asymptomatic bradycardia during the 24-hour Holter ECG recording. Therefore, we conclude that oral propafenone is effective at a dose range of 300 to 600 mg/day is effective and safe in the suppression of frequent ventricular extrasystoles in patients with functionally normal heart.(Tzu Chi Med J 1997;9:259-264)

Avoiding drug problems. The safety of drugs for supraventricular tachycardia.

To minimize drug problems in the treatment of supraventricular tachycardias, it is important to understand the spectrum of adverse events and to identify patients at high risk for these problems. Adverse cardiac and non-cardiac effects are associated, to varying degrees, with currently available antiarrhythmics. Cardiac adverse events include the development of rhythm disturbances, such as ventricular tachycardia or torsades des pointes, may result in syncope or death. In a meta-analysis of six randomized trials of quinidine vs placebo for atrial fibrillation, 1.8% of quinidine-treated patients died as opposed to 0.3% of placebo-treated patients. This increase in mortality was also noted in patients enrolled in the Stroke Prevention in Atrial Fibrillation Trial who were treated with type I antiarrhythmics. This increase in mortality was confined primarily to patients with a history of congestive heart failure. In a randomized trial of propafenone and sotalol for the treatment of atrial fibrillation, two out of 50 patients receiving sotalol died suddenly, one of whom had hypokalaemia-associated torsades des pointes. No patient receiving propafenone died during this trial. In a meta-analysis of propafenone's effect in treating supraventricular tachyarrhythmias in over 3100 adult patients, overall mortality was extremely low at 0.3%. Structural heart disease may increase the risk of antiarrhythmic agents. During inpatient drug trials in patients treated for atrial fibrillation at Brigham and Women's Hospital, adverse cardiac events, primarily bradyarrhythmias, occurred in up to 15% of the patients. Older age and prior myocardial infarction were associated with an increased risk of adverse events. Adverse drug problems may be minimized by careful attention to electrolytes, medications, concomitant medical illnesses, and underlying conduction disease. Careful monitoring of patients during initiation of therapy, especially those patients with ischaemic heart disease, congestive heart failure, and who are older, may minimize drug-related problems.

Inhibition of L-type calcium current by propafenone in single myocytes isolated from the rabbit atrioventricular node.

1. The atrioventricular node (AVN) is an important part of the conduction system in the heart and is a significant site of antiarrhythmic drug action. The class 1 antiarrhythmic propafenone is effective in treating a variety of arrhythmias, including those involving the AVN. In this study, we have investigated the effects of propafenone on ionic currents in single rabbit AVN cells, focusing in particular on those on L-type calcium current (ICa,L). 2. With a standard K-based internal dialysis solution, exposure to 5 microM propafenone reduced significantly the amplitude of ICa,L. In spontaneously active AVN myocytes, action potential upstroke velocity was decreased by propafenone exposure, consistent with the observed change in ICa,L. 3. By use of a Cs-based internal dialysis solution to record ICa,L selectively, voltage clamp test pulses were applied from a holding potential of -40 mV to +10 mV (stimulation frequency 0.33 Hz). Propafenone 5 microM reduced mean ICa,L density at +10 mV from -9.58 +/- 1.05 pA/pF to -4.19 +/- 0.60 pA/pF (P < 0.002). A range of propafenone concentrations were applied which reduced ICa,L in a dose-dependent manner (IC50 1.7 microM). When test pulses were applied to a range of potentials, propafenone reduced ICa,L at each potential without significantly affecting the activation curve for this current. Thus, propafenone reduced ICa,L conductance, without affecting the voltage-dependent activation properties of the current. 4. ICa,L block by propafenone exhibited tonic-, use- and frequency-dependent characteristics. 5. In the presence of propafenone, the voltage-dependence of inactivation of ICa,L was shifted 8 mV in the hyperpolarizing direction. Also, the recovery of ICa,L from inactivation was slowed by propafenone. 6. The ICa,L blocking properties of propafenone may mediate some of the antiarrhythmic properties of this agent, particularly in regions of the heart such as the AVN in which ICa,L contributes significantly to the action potential upstroke.

Cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in the conscious dog

We studied the cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in conscious dogs. Sinus rate, corrected sinus recovery time and Wenckebach point were measured in 6 intact dogs. Atrial rate, ventricular rate and atrial effective refractory period were measured in 6 atrioventricular-blocked dogs. In both groups, we also determined blood pressure and plasma drug concentrations. Each dog received, with at least an 8-day interval, propafenone (hydrochloride) and 5-hydroxypropafenone (hydrochloride) in 4 successive intravenous injections, 30 min apart, at 0.5, 0.5, 1 and 2 mg kg −1. Propafenone increased sinus rate and atrial rate more markedly than 5-hydroxypropafenone, and also transiently ventricular rate, whereas 5-hydroxypropafenone decreased it weakly. Propafenone shortened corrected sinus recovery time and increased Wenckebach point at the highest dose only, whereas 5-hydroxypropafenone did not modify corrected sinus recovery time and increased Wenckebach point less markedly than propafenone. Both drugs produced an identical atrial effective refractory period lengthening. Propafenone either increased mean blood pressure (in intact dogs) or decreased it (in atrioventricular-blocked dogs) at the highest dose only, whereas 5-hydroxypropafenone did not produce any effect on this parameter. Overall, these results show that propafenone and 5-hydroxypropafenone exhibit cardiac electrophysiological effects, reflecting (a) direct vagolytic action for both drugs associated with cardiodepressant effects for 5-hydroxypropafenone, and (b) marked atrial antiarrhythmic properties for 5-hydroxypropafenone probably involved in the therapeutic effect of propafenone.

Effects of oral propafenone on defibrillation and pacing thresholds in patients receiving implantable cardioverter-defibrillators

The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.

Effects of propafenone on the median frequency of ventricular fibrillation in Langendorff perfused guinea-pig hearts

Effects of propafenone on the median frequency of ventricular fibrillation in Langendorff perfused guinea-pig hearts

Effects of propafenone on the median frequency of ventricular fibrillation in Langendorff perfused guinea-pig hearts

The aim was to investigate the antifibrillatory effects of two concentrations of propafenone by means of signal analysis of epicardial ECG recordings in isolated, Langendorff-perfused guinea-pig hearts. Isolated Langendorff-perfused guinea-pig hearts were used as a model for sustained ventricular fibrillation (VF) during reperfusion after global ischaemia. ECG signals were recorded for the first 20 min of reperfusion. The recording was divided into episodes of 1 s and the median frequency (FM) of the dynamic power spectrum was computed for each episode. Cardiac electrical activity was monitored for an additional 10 min. Additionally steady state conditions (i.e. constant FM values for the remaining observation period) were analysed and the effects of 0.1 microM and 1.0 microM propafenone added at reperfusion on the FM were examined. After initial irregularities, FM remained on a high steady state level in the control group. The addition of propafenone altered the steady state value of FM in a dose-dependent and significant manner but had no effects on the time until steady state was reached. During reperfusion without propafenone, 1 out of 6 hearts spontaneously converted to a stable sinus rhythm. Reperfusion with 0.1 microM propafenone caused spontaneous conversion to stable sinus rhythm in 1 out of 6 hearts and intermittent periods of sinus rhythms in 2 additional hearts. During the first 30 min of reperfusion with 1.0 microM propafenone, 5 out of 6 hearts spontaneously converted to stable sinus rhythm. The sixth heart showed repeated switching between VF and periods of non-sustained sinus rhythm. Propafenone caused a dose-dependent decrease of FM at steady state conditions. The rate of spontaneous termination of VF appeared to be dose dependent and the stability of the sinus rhythm was correlated inversely with the FM immediately before spontaneous defibrillation. Therefore, in this model the FM value prior to spontaneous termination of VF may be useful in the estimation of defibrillation success.

Rate-dependent effects of detajmium and propafenone on ventricular conduction and refractoriness in isolated guinea pig hearts.

Detajmium (4--3'-diethylamino-2'-hydroxypropyl--ajmalin) is an Na(+)-channel-blocking drug with an extremely long recovery from use-dependent sodium channel block. The aim of the present study was to investigate the rate-dependent effects of detajmium on the intraventricular conduction of isolated, spontaneously beating, guinea pig hearts in comparison with the effects of propafenone. Detajmium (0.3 microM) and propafenone (0.3 microM) caused comparable prolongations of the intraventricular conduction time during sinus rhythm. The time to steady state of the rate-dependent QRS prolongation during rapid ventricular pacing follows an exponential function of the beat number after an abrupt change of frequency and is characterized by a drug-specific time constant. This time constant was significantly longer for detajmium (tau = 265 +/- 165 beats; mean +/- SEM; n = 6) than for propafenone (tau = 31 +/- 4 beats; n = 11; p < 0.01). In the presence of propafenone, QRS duration peaked initially before decreasing to a steady state. Detajmium, in contrast, progressively broadened the QRS complex. Both substances caused the greatest increase in the ventricular effective refractory period (V-ERP) when the number of conditioning stimuli (interstimulus interval, 120 ms) was in the range of the time constant. However, when the number of conditioning stimuli was further increased, the V-ERP for propafenone diminished progressively. In conclusion, propafenone displayed, in comparison with detajmium, only a transient rate-dependent effect on intraventricular conduction and V-ERP.

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.

Propafenone Preferentially Blocks the Rapidly Activating Component of Delayed Rectifier K + Current in Guinea Pig Ventricular Myocytes

The effects of propafenone on the delayed rectifier K+ current were studied in guinea pig ventricular myocytes by using the patch-clamp technique. In these myocytes, this current consists of at least two components: a La(3+)-sensitive component activating rapidly with moderate depolarizations and a La(3+)-resistant current slowly activating at more positive potentials. In the absence of La3+ (when both components are present), propafenone inhibited the delayed outward current, its effects being more marked after weak than after strong depolarizations. Propafenone-induced block of the tail currents elicited on return to -30 mV was more marked after short than after long depolarizing pulses. In the presence of 1 mumol/L propafenone, the envelope-of-tails test was satisfied, thus indicating that at this concentration propafenone completely blocks the rapidly activating component. In the presence of La3+ (when only the slow component is present), the steady state inhibition induced by 5 mumol/L propafenone on both the maximum activated and the tail currents was independent of the test pulse voltage. Development of propafenone-induced block on the slowly activating component was very fast and linked to channel opening. In addition, the blockade appeared to be use dependent, with the rate constant of the onset kinetics at 2 Hz being 0.44 +/- 0.1 pulse-1. The recovery process from propafenone-induced block exhibited a time constant of 2.5 +/- 0.4 s. These results indicated that propafenone preferentially inhibits the rapidly activating component of the delayed rectifier and that it blocks in a voltage-independent and time-dependent manner the slow component of this current.

Neurotoxic action of some antiarrhythmic agents: comparative effects of propafenone, lidocaine and amiodarone on leech Retzius nerve cell

A series of antiarrhythmic drugs was studied on spontaneous spike activity and depolarizing outward potassium current in leech Retzius nerve cells. Propafenone (0.7 μM/ml) produced a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated after 250 msec by a rapid repolarization. The effect of lidocaine (0.7 μM/ml) on spontaneous spike activity was less pronounced, and early afterdepolarization has been recorded. Amiodarone at the same and much higher concentrations (3 μM/ml) did not generate either a cardiac-like action potential or an early afterdepolarization. In the voltage clamp experiments, fast and slow calcium-activated outward potassium currents were suppressed with propafenone and lidocaine but not with amiodarone. These results suggest that the antiarrhythmic drugs, propafenone and lidocaine modulate calcium-activated potassium channels in leech Retzius nerve cells.

Effects of propafenone and combined disopyramide and metoprolol in patients with supraventricular tachyarrhythmias and WPW syndrome

Effects of propafenone and combined disopyramide and metoprolol in patients with supraventricular tachyarrhythmias and WPW syndrome

Voltage‐ and time‐dependent inhibitory effects on rat aortic and porcine coronary artery contraction induced by propafenone and quinidine

1. Class I antiarrhythmic drugs (e.g. Na+ channel blockers) such as propafenone and quinidine also inhibit voltage-gated Ca2+ and K+ channels. In the present paper the voltage- and time-dependent inhibitory effects of propafenone and quinidine were studied on depolarization-induced vascular contractions and 45Ca2+ uptake in isolated endothelium denuded rat aorta and pig left descending coronary artery. 2. Quinidine and propafenone (10(-7) M -5 x 10(-5) M) produced a concentration-dependent relaxation of the contractions induced by 80 mM KCl. Propafenone was significantly more potent (P < 0.05) than quinidine in both rat aorta and pig coronary arteries but both drugs more potent (P < 0.05) in relaxing rat aorta than pig coronary arteries. In rat aortic rings, the relaxant effects of propafenone were unaffected by pretreatment with the Na+ channel blocker, tetrodotoxin. 3. The degree of inhibition produced after prolonged exposure (40 min) to propafenone and quinidine differed as the time of depolarization with 80 mM KCl was increased. Quinidine (3 x 10(-6) M, 10(-5) M and 3 x 10(-5) M) not only produced an inhibition at the very early stage of contraction, but also a time-dependent inhibition was observed. In contrast, propafenone (10(-6) M, 3 x 10(-6) M and 10(-5) M) produced a more marked concentration-dependent early block but only a mild time-dependent inhibition.4. The voltage-dependence of propafenone- and quinidine-induced inhibition, was studied in rat aorta and coronary arteries which had been incubated in 5 or 40mM KCl Ca2+-free solution and then contracted by changing the bath solution to 100 mM KCI and 2 mM CaCl2 solution. The inhibitor effects of quinidine were significantly enhanced (P <0.05) when the preparations were preincubated in 40 mMKCl (depolarizing) solution. In contrast, the effects of propafenone were quite similar in 5 or in 40 mMKCI solution.5. Quinidine, 10-5 M, produced a greater inhibition (P<0.05) of 100 mM KCl-stimulated 45Ca2+ uptake in aortic rings preincubated in depolarizing as compared to normal solution. In contrast, the inhibition produced by 3 x 10-6 M propafenone was similar in aortic rings incubated in 5 or 40 mM KCl solution.6.It is concluded that both quinidine and propafenone inhibited vascular smooth muscle contraction which could be attributed to reduced Ca2+ entry. The voltage- and time-dependent inhibitory effects of quinidine may reflect an increased binding of the drug to Ca2+ channels at depolarized potentials.