[Treatment of atrial fibrillation in a Hungarian hospital department of cardiologic internal medicine at the turn of the millennium]. / Törekvés a pitvarfibrilláció ritmuskontroll-kezelésére kardiológiai profilú belgyógyászati osztályon az ezredfordulón.

INTRODUCTION: The atrial fibrillation is a severe and frequent disease, which influences greatly the patients' quality of life. Only a few Hungarian studies exist which discuss the physicians' own experiences in its treatment. AIM: The description of the experiences acquired in an internal medicine department with cardiological profile during the treatment based on the actual guidelines and the review of the results of one year follow-up. METHOD: Retrospective analysis of the data of patients treated with atrial fibrillation between 1 january 1999 and 31 december 2001 and a one year follow-up was performed. The age, gender, success in cardioversion, the antiarrhythmic therapy at the discharge and the modification in it during the first year were evaluated. RESULTS: During the 3 years long period 1115 patients with atrial fibrillation were admitted (53.9% female, 46.1% male, the mean age was 72.0 +/- 10.4 years), 391 of whom were discharged with sinus rhythm. In 193 cases (49%) a spontaneous cardioversion was observed. 120 electrical (31%) and 78 pharmacological (20%) cardioversions were performed. The electrical form was carried out in 42 cases with acute atrial fibrillation (in 36 of them successfully) and in 100 cases as an elective procedure, in 84 successfully. Pharmacological cardioversion was made in 39 acute cases with the administration of propafenone (in 29 ones successfully) and in 57 elective cases with quinidine + beta-blocker + magnesium (in 49 ones successfully). For the maintenance of sinus rhythm in the 38.8% of cases amiodarone, 24.0% propafenone, 19.9% sotalol, 10.7% beta-blocker, 0.8% quinidine, 0.5% prajmaline was administered, and 5.1% of the patients didn't receive any special treatment. During the one year follow-up from the 391 patients 261 remained on sinus rhythm, in 81 cases (21%) the return of the atrial fibrillation was diagnosed (in 57 of them a successful cardioversion was performed again), 11 patients (3%) died and 38 (9%) were lost for observation. At the time of the one year control 57.8% of patients treated with amiodarone, 61.7% of those treated with propafenone, 67.9% with sotalol and 35.7% with beta-blocker remained on sinus rhythm. The amiodarone was omitted in 17 cases because of its side effects. CONCLUSIONS: The treatment of the atrial fibrillation has to be performed individually taking into account the guidelines, the comorbidity, the time of the beginning of rhythm disorder, the patients' present other drugs and the former antiarrhythmic therapy. A continuous and consistent follow-up of these patients is crucial.

[Antiarrhythmic effects of prajmaline (Neo-Gilurythmal) in stable angina pectoris in light of Holter electrocardiographic monitoring]. / Przeciwarytmiczne efekty prajmaliny (Neo-Gilurytmal) w stabilnej dusznicy bolesnej w swietle holterowskich badan elektrokardiograficznych.

40 patients with various type of arrhytmia with stable angina were treated with 3 x 20mg Prajmalin (Neo-Gilurytmal) over 6-day period. A positive antyarhytmic response was observed in 30 patients (75%). In the remaining 10 patients considering the lack of adequate response after 6 days on 60 mg the trial was continued at a dose of 100 mg/day (5 x 20mg). With this dose bringing on the desired results. In 32 patients with VE'e and SVE's Neo-Gilurytmal was used in mono therapy. While in other types of arthymia it was used as previously as a first treatment and also in cases where other antiarhytmic drugs (e.g. Propahenone, Mexitil or Beta-blockers) were unsuccessful. Antiarhytmic effects were verified using 24-hour Holter monitoring before introduction of Neo-Gilurytmal, during the first fourth and seventh day of administration and also the eleventh day of observation (in 30 patients three days after cessation of treatment and in 10 cases three days after commencing on 100 mg daily). The results, as mean of the 24-hour observation was statistically analysed using the Wilcoxon test. We analysed the mean from the first day (H1), fourth day (H2), seventh day (H3) i.e. 6 days after administration and in 10 patients three day after increasing the dose to 100 mg/day (H4). We compared this to a base value (Ho) obtained before drug administration. The results obtained showed the Neo-Gilurythmal is an effective drug significantly reducing meanly VE's and SVE's and also gigemini, trigemini, coupled, runs. It was concluded that Neo-Gilurythmal did not significantly effect the heart rate and QT intervals and also QT adjusted to the heart rate. It was also noticed that these was a lack of therapeutic effect 3 days after cessation of treatment, which was suggested that constant therapy is required. Neo-Gilurythmal was find to be effective even in the case where other previously used antiarhymics were ineffective. We also observe a positive result in treatment of paroxismal tachycardia, in treatment of WPW Syndrome and also in prophylactic againts its recurrence. In our study no adverse effects (e.g. cardiac muscle depression, hypotensive episodes or noted in other studies gepatotoxicity or cholestatic episodes) were observed.

[Magnesium or proajmaline (neogilurytmal) in treatment of recurrences of paroxysmal supraventricular tachyarrhythmias?]. / Magnez czy proajmalina (neogilurytmal) w leczeniu nawrotów napadowych tachyarytmii nadkomorowych?

In order to compare the effectiveness of magnesium with that of proajmaline in preventing of recurrences of paroxysmal tachyarrhythmias. 60 consecutive patients were studied who had been previously treated for paroxysmal arterial fibrillation (PAF) or paroxysmal supraventricular tachycardia (PSVT). For the studies the patients were qualified who had been effectively treated during acute phase with intravenous magnesium (magnesium sulphate) and ajmaline (gilurytmal). The patients were randomly divided into three groups of 20 persons in each, every group received different oral treatment: in the first group--magnesium (magnesium carbonate) 3 x 0.6, in the second--proajmaline (neogilurytmal) in dose 3 x 20 mg, and in the third--neogilurytmal 2 x 20 mg and magnesium 2 x 0.6. During three months of observation the effectiveness of treatment and incidence of adverse effects were assessed. The following was found: neogilurytmal showed higher effectiveness (60%) than magnesium (30%), while the combined treatment demonstrated similar effectiveness (65%) as neogilurytmal alone with lower drug doses and lower incidence of bad tolerance manifestations (10% vs 20%).

Fosfolipasa A2 y su papel en el funcionamiento hepático por acción de prajmalina / Phospholipase A2 and its role in liver function by projaline action

Se estudió la influencia del tiempo de tratamiento con prajmalina sobre las concentraciones plasmáticas de la fosfolipasa A2, y se correlacionaron estos resultados con los niveles de las enzimas creatin fosfoquinasa (CPK) y transaminasa glutamicooxalacética (GOT). Los parámetros enzimáticos exhibieron tendencias semejantes, las cuales disminuían con respecto al tiempo de tratamiento con el antiarrítmico. Cuando se evaluaron las relaciones CPK/fosfolipasa A2 y GOT/fosfolipasa A2 se encontró que estas relaciones eran representativas del momento a partir del cual se producía la lesión orgánica

Fosfolipasa A2 y su papel en el funcionamiento hepático por acción de prajmalina / Phospholipase A2 and its role in liver function by projmaline action

Se estudió la influencia del tiempo de tratamiento con prajmalina sobre las concentraciones plasmáticas de la fosfolipasa A2, y se correlacionaron estos resultados con los niveles de las enzimas creatin fosfoquinasa (CPK) y transaminasa glutamicooxalacética (GOT). Los parámetros enzimáticos exhibieron tendencias semejantes, las cuales disminuían con respecto al tiempo de tratamiento con el antiarrítmico. Cuando se evaluaron las relaciones CPK/fosfolipasa A2 y GOT/fosfolipasa A2 se encontró que estas relaciones eran representativas del momento a partir del cual se producía la lesión orgánica

[Anti-arrhythmic effectiveness of neogilurhythmal in extrasystolic arrhythmia]. / Antiaritmicheskaia éffektivnost' neogiluritmala pri ékstrasistolicheskoi aritmii.

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.

[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]. / Vliianie kombinatsii N-propilaimalinbromida i trimekaina na aritmii serdtsa raznogo geneza i élektrofiziologicheskie parametry miokarda.

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.

[Diagnostic difficulties in prajmaline-induced intrahepatic cholestasis]. / Trudnosci diagnostyczne sródwatrobowego zastoju zólci wywolanego zazywaniem prajmalium.

A case of prajmalium-induced intrahepatic cholestasis is presented. A proper diagnosis was delayed because differential diagnosis did not include toxic liver damage. Pathogenetic considerations included immunological background of the disease which improved completely within one year. No clinical and biochemical complications were seen.

[The anti-arrhythmia action of combinations of N-propylajmaline bromide with anti-arrhythmia agents of different classes]. / Protivoaritmicheskoe deistvie kombinatsii N-propilaimalinbromida s protivoaritmicheskimi preparatami raznykh klassov.

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.

[Modification of blood coagulation by the anti-arrhythmia drug prajmalium bitartrate in vivo]. / Beeinflussung der Blutgerinnung durch das Antiarrhythmikum Prajmaliumbitartrat in vivo.

We studied the effects of prajmaliumbitartrate (PBT, Neo-Gilurytmal, Giulini Pharma, Hannover, FRG), an antiarrhythmic drug on some parameters of blood coagulation in patients. PBT, 20 mg given three times a day, significantly prolonged template bleeding time and ex vivo thrombus formation time in a modified Chandler's loop. Ex vivo platelet aggregation using different agonists and tests of the plasmatic coagulation system remained unchanged.

[Intrahepatic cholestasis and aplastic anemia following administration of prajmaline]. / Intrahepatische Cholestase und aplastische Anämie nach Prajmalin-Einnahme.

Intrahepatic cholestasis and aplastic anemia after N-propylajmaline. A 43 year old female patient taking oral contraceptives for more than five years received the antiarrhythmic drug N-propylajmaline for treatment of ventricular arrhythmia. After twelve days (total dosage 510 mg N-propyl-ajmaline) acute severe intrahepatic cholestasis and aplastic anemia developed. The erythropoeisis improved after three weeks of treatment with corticosteroids. However, despite treatment with phenobarbital the jaundice receded very slowly. Even after nine years of follow-up cholestatic enzymes are still significantly elevated although serum bilirubin levels are in the normal range. This case report demonstrates that antiarrhythmic drugs may induce nearly irreversible intrahepatic cholestasis and severe hematological disturbances.

Pharmacokinetics of n-propyl-ajmaline-bitartrate in elderly patients with ventricular ectopic activity.

11 patients (9m, 2f, median age 59 years) with ventricular ectopic activity of at least Lown grade III received 20 mg N-Propyl-ajmaline-bitartrate (N-PAB) p.o. Plasma concentrations of N-PAB were determined with HPLC from blood samples within 26 hours after administration. An open two-compartment model was used. In 8 patients with normal function of the liver and the kidneys, the median clearance of N-PAB was 6.86 ml/min/kg and the median volume of distribution was 1.56 l/kg. Two patients had a clearly diminished clearance of 1.58 ml/min/kg without obvious impairment of liver or renal function. One patient with chronic glomerulonephritis (plasma creatinine 3.4 mg/dl) had a N-PAB clearance of 2.79 ml/min/kg. None of the Spearman rank correlation coefficients between the pharmacokinetic parameters of N-PAB with age, plasma albumin/globulin-quotient, plasma creatinine and cholin-esterase were significant. All calculated parameters were in the range determined in young subjects. It is concluded that physiological changes with age do not lead to significant changes of the pharmacokinetics of N-PAB. On the other hand in patients with increased levels of plasma creatinine a diminished clearance of N-PAB can be expected. It is also possible that patients without an obvious impairment of liver or renal function may have diminished N-PAB clearance.

[Comparative study of the anti-arrhythmia effect of flecainide acetate and prajmalium bitartrate in patients with tachycardiac ventricular rhythm disorders]. / Vergleichende Untersuchung über den antiarrhythmischen Effekt von Flecainidacetat und Prajmaliumbitartrat bei Patienten mit tachykarden ventrikulären Rhythmusstörungen.

In an open randomized therapeutic study, 20 patients known to have frequent ventricular premature beats (VPB) and/or ventricular pairs (VP) were treated with both 2 X 200 mg flecainide (F) and 4 X 20 mg prajmalium-bitartrate (P) for 3 months each. There was a drug-free interval of one week between the two therapy phases. 24-hour long-term ECG-registrations were carried out before the start of the therapy phases as well as 1 week, 1 month, 2 months and 3 months after the initiation of antiarrhythmic therapy. After one week, the group as a whole evidenced a VPB reduction of 94% under F and only 57% under P (p less than or equal to 0.05). The percentage of individual patients in whom there was a statistically significant VPB reduction was also higher under F than under P (65% vs. 40%). In the group as a whole, there was a VP reduction of 99% under F and 88% under P (p less than or equal to 0.05) after one week. Of the 13 individuals with frequent VP (over 16 VP/24 h), a significant reduction was seen in 77% under F and only 38% under P. The difference between the two antiarrhythmic agents registered after one week was also observed in the further course of therapy but could no longer be statistically confirmed for the ventricular pairs. An aggravation of ventricular arrhythmias was observed in 2 patients under F and in 3 under P.(ABSTRACT TRUNCATED AT 250 WORDS)

[Dose-effect relation of N-prajmalium bitartrate with control of plasma levels]. / Dosis-Wirkungs-Beziehung von N-Prajmaliumbitartrat unter Plasmaspiegelkontrolle.

15 patients with ventricular ectopic beats classified to at least Lown class III with more than 100 ventricular ectopic beats in one hour were treated with N-prajmalium bitartrate (NPAB) in increasing dosages. The first dosage of 4 X 5 mg/d has been increased by 5 mg in three steps of three days to a level of 4 X 20 mg/d. A resting ECG, the systolic time intervals and a 24 h ECG were registered before treatment and after every dose. The median PQ time increased from 170 msec to 200 msec, the increase becoming significant (p less than 0.05) with a dose of 4 X 5 mg/d NPAB and above. Frequency, QRS and the frequency-corrected QT time did not change significantly. At a dose of 4 X 10 mg/d NPAB the increase of the quotient pre-ejection period to ejection time PEP/LVET became significant, increasing continuously from 0.35 to 0.48. Six of the 15 patients showed a significant reduction of ventricular ectopic beats, couplets and salvoes. In two patients the antiarrhythmic effect was significant at 4 X 5 mg/d. With an increasing dose from 4 X 10 mg/d each responder showed a significant reduction of ventricular ectopy. The lowest effective plasma concentrations ranged from 15 to 213 ng/ml with a median value of 58 ng/ml and an upper quartile of 94 ng/ml. There was no significant difference in plasma concentrations between responders and non-responders.