Effects Of Propafenone Research Articles

Development of new Kir2.1 channel openers from propafenone analogues.

Reduced inward rectifier potassium channel (Kir2.1) functioning is associated with heart failure and may cause Andersen-Tawil Syndrome, among others characterized by ventricular arrhythmias. Most heart failure or Andersen-Tawil Syndrome patients are treated with β-adrenoceptor antagonists (β-blockers) or sodium channel blockers; however, these do not specifically address the inward rectifier current (IK1) nor aim to improve resting membrane potential stability. Consequently, additional pharmacotherapy for heart failure and Andersen-Tawil Syndrome treatment would be highly desirable. Acute propafenone treatment at low concentrations enhances IK1 current, but it also exerts many off-target effects. Therefore, discovering and exploring new IK1-channel openers is necessary. Effects of propafenone and 10 additional propafenone analogues were analysed. Currents were measured by single-cell patch-clamp electrophysiology. Kir2.1 protein expression levels were determined by western blot analysis and action potential characteristics were further validated in human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMCs). Molecular docking was performed to obtain detailed information on drug-channel interactions. Analogues GPV0019, GPV0057 and GPV0576 strongly increased the outward component of IK1 while not affecting the Kir2.1 channel expression levels. GPV0057 did not block IKr at concentrations below 0.5μmol L-1 nor NaV1.5 current below 1μmol L-1. Moreover, hiPSC-CMC action potential duration was also not affected by GPV0057 at 0.5 and 1μmol L-1. Structure analysis indicates a mechanism by which GPV0057 might enhance Kir2.1 channel activation. GPV0057 has a strong efficiency towards increasing IK1, which makes it a good candidate to address IK1 deficiency-associated diseases.

Propafenone-induced connexin-43 protein accumulation and intracellular dynamics

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): China Scholarship Council Background Connexin-43 (Cx43) plays a pivotal role in intercellular communication through gap junctions. It is instrumental in propagating electrical signals and allowing ions to flow between neighboring cardiomyocytes. This synchronized electrical activity allows the heart to work as a functional syncytium. Any disruption or malfunction of Cx43 can lead to arrhythmias and other cardiac issues. Understanding the functions and regulation of Cx43 is vital in both basic research and clinical contexts. Propafenone, a class Ic antiarrhythmic drug, has shown promise in rhythm control; however, its precise impact on cardiac cellular physiology, particularly regarding Cx43, remains incompletely understood. Purpose To investigate propafenone’s effect on Cx43 expression, physiology, and underlying mechanisms in cell systems. Methods Used cell lines include human embryonic kidney HEK293 cells transfected with Cx43; differentiated murine embryonic carcinoma EPI7 cells with an epithelioid morphology and visceral endoderm-like END2 cells, endogenously expressing high amounts of functional Cx43. Cx43 protein expression levels were determined by Western blot analysis, whereas immunofluorescence (IF) imaged by a Total Internal Reflection Fluorescence (TIRF) microscope was used to assess the subcellular localization of Cx43 proteins. Dye injections were used to gain insight into the effects of propafenone on Cx43 metabolic coupling. Results and Conclusion Full length Cx43 protein levels were increased after treatment with propafenone and IF microscopy showed an intracellular accumulation of Cx43 protein, both on ectopically and endogenously expressed Cx43. Propafenone did not alter Cx43 half-life, in contrast to the lysosomal inhibitor chloroquine. Finally, gap-junctional coupling was decreased by chronic propafenone treatment. We conclude that the class 1c antiarrhythmic drug propanone increases Cx43 protein expression, resulting in its intracellular accumulation, as a side effect.

The Effects of Propafenone on Postoperative Atrial Fibrillation in Adult Patients Undergoing Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

Background. Previous research has only conducted a restricted amount of investigations on the effectiveness of propafenone in preventing and treating of atrial fibrillation (AF) after cardiac surgery. Hence, a comprehensive evaluation and meta-analysis were performed to evaluate the effectiveness and safety of propafenone in individuals undergoing cardiac surgery for postoperative atrial fibrillation (POAF). Methods. A meta-analysis of randomized controlled trials was conducted. Until September 15th, 2023, various databases were searched. The main focal points consisted of the presence of POAF, transition from AF to sinus rhythm, and reappearance of AF. The odds ratios (ORs) for treatment effects on dichotomous variables were calculated. Results. The analysis of data included 9 controlled trials that were randomized and had 1014 patients. The findings indicated that propafenone has a significant impact on reducing the occurrence of POAF in adult patients who undergo cardiac surgery (OR, 0.52; 95% CI: 0.30, 0.89; P=0.02). In addition, it was observed that propafenone significantly increase the rate of conversion to sinus rhythm from AF within 20 min (OR, 5.39; 95% CI: 2.25, 12.91; P=0.0002) and 1 hour (OR, 2.89; 95% CI: 1.50, 5.57; P=0.002) after administration. Surprisingly, the administration of propafenone treatment did not have a significant impact on the rate of conversion to sinus rhythm from AF within 24 hours (OR, 0.63; 95% CI: 0.38, 1.04; P=0.07) after administration. Conclusions. The present study suggests that the postoperative administration of propafenone to adult cardiac surgery patients is both safe and effective for preventing and treating POAF.

Determinants and therapeutic potential of calcium handling abnormalities in atrial fibrillation: what can we learn from computer models?

Determinants and therapeutic potential of calcium handling abnormalities in atrial fibrillation: what can we learn from computer models?

Comparative effectiveness of propafenone and aksaritmin for conversion of paroxysmal atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Aksaritmin (the sum of nine deterpenoid alkaloids, including lappaconitini hydrobromidum) is an antiarrhythmic drug (conditionally belongs to the I C class) which is extracted from the roots and rhizomes of local plant - Aconitum septentrionale (tablet 25 mg). Purpose Evaluation of comparative effectiveness of propafenone (Pr) and aksaritmin (Aks) for conversion of atrial fibrillation (AF) in patients without/minimal structural heart disease (ejection fraction is more than 50%). Materials and methods The study included 60 patients (31 men), mean age - 55.3±11.9 y.o. The inclusion criteria for patients in the study were: hemodynamically stable symptomatic paroxysmal AF (mean duration–16.3±9.1 hours). On the day of admission, all patients underwent a test of the necessary biochemical blood parameters, electrocardiography, 24-hour ECG monitoring, transthoracic echocardiography. The patients were divided into two groups (they did not differ in the main clinical and anamnestic characteristics): 1-group (n=30), Pr was prescribed in dose 450-600 mg per os; 2-group (n=30), Aks was prescribed in dose 50 mg (in combination with beta-blockers (60%) in cases of tachysystole (≥ 140 b.p.m.)) per os. Statistical analysis was carried out by the STATISTICA 13. Results The main causes of AF in group 1 and group 2: hypertension - 17 (56.7%) and 16 (53.3%), chronic persistent myocarditis - 11 (36.7%) and 12 (40%), idiopathic AF - 2 (6.7%) and 2 (6.7%) patients, respectively. The anamnesis of AF averaged 17.3±3.8 months in gr 1 and 18.2±4.7 months in gr 2. Pr according to the above-described scheme ("pill in a pocket"), sinus rhythm was restored in 22 (73.3%) of 30 patients, and the mean time to restore the sinus rhythm was 4.12±3.87 hours from the start of therapy. At the same time, the effectiveness of Pr in patients with a paroxysm duration of less than 24 hours was 77.2% - in 17 patients out of 22, with a duration 24-48 hours it was 62.5% - 5 patients out of 8. Aks restored sinus rhythm in 21 (70%) out of 30 patients (χ2=0.082; p>0.05), and the mean restoring time of sinus rhythm was 4.63±4.33 hours from the start of therapy (p>0.05). At the same time, the effectiveness of Aks in patients with a paroxysm duration of less than 24 hours was 81.8% - in 18 patients out of 22 (χ2=0.140; p>0.05), with a duration of more than 24-48 hours it was 37.5%-3 patients out of 8 (χ2=1.000; p>0.05). Conclusion Pr and Aks practically did not differ in efficiency (73.3% and 70%, respectively) and in the time of relief (4.12±3.87 h and 4.63±4.33 h, respectively) of AF paroxysms. At the same time, Aks (including combination with beta-blockers) was more preferable for relief of AF with a duration of up to 24 hours-81.8% versus 77.2% (p>0.05), and propafenone for relief of AF with a duration of more than 24-48 hours-62.5% versus 37.5% (p>0.05). Aks is relatively new and promising drug for the treatment of patients with new onset paroxysmal AF.

Electrophysiological effects and clinical utility of propafenone in children.

This retrospective case series study sought to describe the safety and clinical effectiveness of propafenone for the control of arrhythmias in children with and without CHD or cardiomyopathy. We reviewed baseline characteristics and subsequent outcomes in a group of 63 children treated with propafenone at 2 sites over a 15-year period Therapy was considered effective if no clinically apparent breakthrough episodes of arrhythmias were noted on the medication. Sixty-three patients (29 males) were initiated on propafenone at a median age of 2.3 years. CHD or cardiomyopathy was noted in 21/63 (33%). There were no significant differences between demographics, clinical backgrounds, antiarrhythmic details, side effect profiles, and outcomes between children with normal hearts and children with CHD or cardiomyopathy. Cardiac depression at the initiation of propafenone was more common amongst children with CHD or cardiomyopathy compared to children with normal hearts. Systemic ventricular function was diminished in 15/63 patients (24%) prior to starting propafenone and improved in 8/15 (53%) of patients once better rhythm control was achieved. Other than one child in whom medication was stopped due to gastroesophageal reflux, no other child experienced significant systemic or cardiac side effects during treatment with propafenone. Propafenone achieved nearly equal success in controlling arrhythmias in both children with normal hearts and children with congenital heart disease or cardiomyopathy (90% versus 86%, p = 0.88). Propafenone is a safe and effective antiarrhythmic medication in children.

Safety of propafenone application in patients with organic myocardial pathology at the prehospital stage

In the course of the study, a group of patients with paroxysms of atrial fibrillation and organic myocardial pathology was identified, who were treated with the antiarrhythmic 1C class propafenone at the pre-hospital stage to control the rhythm. The effect of propafenone on hemodynamics in patients with and without organic myocardial pathology was compared.

Inhibitory effect of propafenone on vortioxetine metabolism in vitro and in vivo

Vortioxetine, as a new therapeutic drug of major depressive disorder (MDD), was approved for MDD in the USA. The significance of our study in this paper was to explore the inhibitory effect of propafenone on the metabolism of vortioxetine through the in vivo and in vitro experiments. In the vitro experiments, we added a series of concentrations of propafenone into an incubation system as the inhibitors and calculated the half-maximal inhibitory concentration (IC50) of propafenone on vortioxetine metabolism in human liver microsomes (HLMs) and rat liver microsomes (RLMs). Twelve male Sprague-Dawley (SD) rats were included in the vivo experiments. We randomly divided them into Group A (control group) and Group B (90 mg/kg propafenone). 30 min later, a single oral dose of 4.0 mg/kg vortioxetine was administrated to each rat. Then, we used ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of vortioxetine and its metabolite Lu AA34443. From our results, it indicated that propafenone inhibited the metabolic rate of vortioxetine in the vitro studies with the IC50 of 0.48 μM and 16.5 μM for HLMs and RLMs, respectively. And, propafenone could competitively inhibit vortioxetine in both HLMs and RLMs for the inhibitory mechanisms. Moreover, a single oral dose of 90 mg/kg propafenone obviously enchanced the exposure of vortioxetine in rats, but not Lu AA34443. Combined with the vitro and vivo data, propafenone showed the inhibitory effect on vortioxetine metabolism. Thus, more attention to the safety of vortioxetine in clinic should be paid when taking it with propafenone in combination for the therapy.

Atrial resting membrane potential confers sodium current sensitivity to propafenone, flecainide and dronedarone

BackgroundAlthough atrial fibrillation ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs is highly variable. Previous work from our group suggests that alterations in atrial resting membrane potential (RMP) induced by low Pitx2 expression could explain the variable effect of flecainide.ObjectiveThe purpose of this study was to assess whether alterations in atrial/cardiac RMP modify the effectiveness of multiple clinically used AADs.MethodsThe sodium channel blocking effects of propafenone (300 nM, 1 μM), flecainide (1 μM), and dronedarone (5 μM, 10 μM) were measured in human stem cell–derived cardiac myocytes, HEK293 expressing human NaV1.5, primary murine atrial cardiac myocytes, and murine hearts with reduced Pitx2c.ResultsA more positive atrial RMP delayed INa recovery, slowed channel inactivation, and decreased peak action potential (AP) upstroke velocity. All 3 AADs displayed enhanced sodium channel block at more positive atrial RMPs. Dronedarone was the most sensitive to changes in atrial RMP. Dronedarone caused greater reductions in AP amplitude and peak AP upstroke velocity at more positive RMPs. Dronedarone evoked greater prolongation of the atrial effective refractory period and postrepolarization refractoriness in murine Langendorff-perfused Pitx2c+/– hearts, which have a more positive RMP compared to wild type.ConclusionAtrial RMP modifies the effectiveness of several clinically used AADs. Dronedarone is more sensitive to changes in atrial RMP than flecainide or propafenone. Identifying and modifying atrial RMP may offer a novel approach to enhancing the effectiveness of AADs or personalizing AAD selection.

Experience of using propafenone in newborns and young children with arrhythmias

Aim. To evaluate the efficacy and safety of propafenone therapy in newborns and young children, including children with congenital heart defects (CHD). Material and methods . The study included 65 children with initiation of propafenone therapy at the age of 0-5 years. For diagnosis of arrhythmias and treatment control, electrocardiography (ECG), 24-hour Holter monitoring and echocardiography were performed. The initial dose of propafenone was 5-7 mg/kg/ day; the maximum dose — 15 mg/kg/day. The dose was titrated to effective with clinical and ECG control. It was considered acceptable to increase the duration of PQ interval and QRS complex by no more than 25% of the baseline value. The adverse and arrhythmogenic effects of the drug were evaluated. Results. Indications for propafenone administration were atrial tachycardia in 29 (44,61%) children, frequent premature ventricular contractions and ventricular tachycardia in 13 (20%) children, Wolff-Parkinson-White syndrome in 13 (20%) children, and other types of supraventricular tachycardia in 10 (15,39%) children. Sixteen (24,62%) children had CHD. In 20 (30,77%) children, propafenone was administrated in the neonatal period. The duration of propafenone therapy was 17,3±15,16 months. The drug was effective in 39 (60%) children (81,25% with CHD and 53,06% without CHD), not effective enough in 14 (21,54%) children, ineffective in 12 (18,46%) children. There was no association of the effectiveness/inefficiency of propafenone depending on the age, sex and the type of arrhythmia. Five (7,69%) children had prolongation of PQ interval and/or QRS by more than 25%. Arrhythmogenic effect of propafenone was observed in 1 (1,54%) child, noncardiac adverse effects — in 3 (4,62%) children. There were no cases of sudden cardiac death. Conclusion. Propafenone is an effective antiarrhythmic drug in newborns and young children with supraventricular and ventricular arrhythmias, including children with CHD. Using propafenone may be accompanied with adverse and arrhythmogenic effects, which were observed in 6% of children and were not associated with CHD.

Propafenone effects on the stable structures of Aβ16-22 system

An extensive replica exchange molecular dynamics (REMD) simulation was performed to investigate the progress patterns of the molecular interactions of propafenone and Aβ16-22 system. Distinct conformational equilibrium of Aβ16-22 system with and without propafenone was analyzed in detail. Propafenone can act to prevent the Alzheimer’s disease (AD) by significantly inhibiting Aβ oligomerization. Our calculated results provide insights into the inhibition mechanism of propafenone on the oligomerization process to form Aβ16-22 peptide aggregation. These findings are valuable for the development of therapeutic drugs in the AD early stage.

Inhibition of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone.

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent K+ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent IC50 value of 5.04±1.05 µM and a Hill coefficient of 0.78±0.06. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of Na+ channel inhibition.

Influence of propafenone on the anticonvulsant activity of various novel antiepileptic drugs in the mouse maximal electroshock model.

The main mechanism of action of propafenone (antiarrhythmic drug) involves the inhibition of the fast inward sodium current during phase 0 of the action potential. Sodium channel-blocking activity is also characteristic for some antiepileptic drugs. Therefore, it could be assumed that propafenone may also affect seizures. In the present study, we evaluated the effect of propafenone on the protective effect of oxcarbazepine, lamotrigine, topiramate and pregabalin against the maximal electroshock-induced seizures in mice. Anticonvulsant activity of propafenone was assessed with the maximal electroshock seizure threshold (MEST) test. Influence of propafenone on the anticonvulsant activity of antiepileptic drugs was estimated in the mouse maximal electroshock model (MES). Drug-related adverse effects were determined in the chimney test (motor coordination) and passive-avoidance task (long-term memory). Brain concentrations of antiepileptics were assessed by fluorescence polarization immunoassay. Propafenone at doses 60-90mg/kg significantly increased the threshold of seizures, in turn at doses 5-50mg/kg did not affect this parameter. Administration of propafenone at the subthreshold dose of 50mg/kg increased antielectroshock activity of oxcarbazepine, topiramate and pregabalin, but not that of lamotrigine. As regards adverse effects, propafenone alone and in combination with antiepileptic drugs did not significantly impair motor coordination or long-term memory in mice. Propafenone (50mg/kg) significantly increased the brain level of pregabalin. Brain concentrations of topiramate and oxcarbazepine were not affected. Our findings show that propafenone has own anticonvulsant action and enhances efficacy of oxcarbazepine, topiramate and pregabalin, but not that of lamotrigine, at least in experimental condition.

ТHE USE OF PROPAFENONE FOR PHARMACOLOGICAL CARDIOVERSION OF PAROXYSMAL ATRIAL FIBRILLATION AT PREHOSPITAL STAGE

This study demonstrates the effectiveness of propafenone for pharmacological cardioversion in patients with paroxysmal atrial fibrillation. Propafenone was used in the recommended dosage 2 mg/kg. The restoration of the sinus rhythm within 60 minutes was observed in 73,2% of cases.

Propafenone enhances the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model.

Antiarrhythmic and antiepileptic drugs share some mechanisms of actions. Therefore, possibility of interactions between these in epileptic patients with cardiac arrhythmias is quite considerable. Herein, we attempted to assess interactions between propafenone and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital. Effects of propafenone on seizures were determined in the electroconvulsive threshold test in mice. Interactions between propafenone and antiepileptic drugs were estimated in the model of maximal electroshock. Motor coordination was evaluated in the chimney test, while long-term memory in the passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay. Propafenone up to 50mg/kg did not affect the electroconvulsive threshold, significantly enhancing this parameter at doses of 60-90mg/kg. Applied at its subthreshold doses, propafenone potentiated the antielectroshock action of all four tested classical antiepileptics: carbamazepine, valproate, phenytoin, and phenobarbital. Propafenone alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Propafenone did not change brain concentration of phenytoin and phenobarbital; however, it significantly decreased brain levels of carbamazepine and increased those of valproate. Propafenone exhibits its own anticonvulsant effect and enhances the action of classical antiepileptic drugs against electrically induced convulsions in mice. Further investigations are required to determine the effect of propafenone on antiepileptic therapy in humans.

Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents

We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now.

The effect of propafenone on the anticonvulsant action of carbamazepine and valproate in the mouse model of maximal electroshock

The effect of propafenone on the anticonvulsant action of carbamazepine and valproate in the mouse model of maximal electroshock

The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta

The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.

Abstract 136: Changes of Myocardial Contractility in Hypertensive Patients With Persistent Atrial Fibrillation Receiving Propafenone

Objective: To study the effect of propafenone 450 mg daily on myocardial contractility in hypertensive patients with persistent atrial fibrillation (AF). METHODS: Study included 32 hypertensive patients with persistent AF, aged from 39 to 63 years (median age 58,6±5,3 years), 14 of them (44%) were men and 18 (56%) were women. Sinus rhythm was restored within 24 hours after the oral loading dose of propafenone 600 mg in all the patients. All the patients received propafenone 450 mg daily to prevent AF paroxysms during the next 12 months. Planar equilibrium radionuclide ventriculography was performed in all the patients to assess myocardial function. Initial study was performed in 32 (100%) patients within the first 3 days after sinus rhythm restoration, the follow-up imaging study was carried out in 18 (56%) patients with sustained sinus rhythm after 12 months. Results: After 12 months of treatment with propafenone, 18 (56%) of hypertensive patients remained in sinus rhythm. Recurrent episodes of AF were registered in 14 (44%) patients during 12 month follow-up period, hence they were excluded from the study. Initial radionuclide ventriculography made after sinus rhythm restoration in hypertensive patients with persistent AF demonstrated myocardial diastolic dysfunction manifested as significant decrease of time to 30% filling and peak LV and RV filling rate. Follow-up study after propafenone treatment during 12 months revealed significant increase in time to 30% filling and peak LV and RV filling rate. Normal values of atrial contribution to left and right ventricular filling were observed in patients maintaining sinus rhythm during 12 month treatment period with propafenone (p<0.05). Systolic parameters and volume of both ventricles remained normal and showed no significant changes. Left and right ventricular ejection fraction before the treatment start and after propafenone administration during 12 months remained within the normal range. Conclusion: Propafenone 450 mg daily administered for recurrent AF prevention does not affect left and right ventricular contractility. Sinus rhythm maintenance for 12 months in hypertensive patients with persistent AF restores atrial contractility and improves ventricular diastolic function.

The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta

Our aim was to define how different chemical properties of newly developed phenylpropiophenone derivates (PhPds) influenced their potency and efficacy to relax rat aorta. A contribution of ion channels in the PhPds and propafenone mechanism of vasodilatation was tested. PhPds were syntethysed by substitution in the benzyl moiety with -F, -CH3 or -CF3 groups on the ortho or para position. The vasodilatation by PhPds was examined on the rings of rat aorta precontracted with phenylephrine. In order to test involvement of voltage-gated Na+ and K+ channels and L-type Ca2+ channels in a mechanism of action of PhPds, we used their blockers: lidocaine, nifedipine and 4-aminopiridine, respectively. Aorta was more sensitive to 5-ortho-trifluoromethyl derivate than to propafenone and other PhPds. The 5-para-methyl derivate had lower potency and efficacy than propafenone and other PhPds. Lidocaine did not influenced relaxation induced by PhPds, but slightly inhibited the effect of propafenone. The 4-aminopiridine only inhibited relaxation induced by 5-para-methyl derivate. Nifedipine inhibited relaxation of the rat aorta induced by 5-ortho-trifluoromethyl derivate and by propafenone. Introduction of 5-ortho-trifluoromethyl and 5-para-methyl group in the benzyl moiety of propafenone molecule changed its potency, efficacy and mechanism of action in the rat aorta. The 4-aminopiridine- and nifedipine sensitive ion channels are involved in mechanism of action of 5-para-methyl and 5-ortho-trifluoromethyl derivate. The introduction of other tested groups in the benzyl moiety does not affect pharmacological properties of the PhPds in relation to propafenone.