Search

Alterations of normal intra- and interatrial conduction are a common outcome of multiple cardiovascular conditions. They arise most commonly in the context of advanced age, cardiovascular risk factors, organic heart disease, atrial fibrosis, and left atrial enlargement. Interatrial block (IAB), the most frequent and extensively studied atrial conduction disorder, affects up to 20% of the general primary care population. IAB can be partial (P wave duration ≥ 120 ms on any of the 12 ECG leads) or advanced (P wave ≥ 120 ms and biphasic morphology (positive-negative) in inferior leads). Advanced IAB is an independent risk factor for supraventricular tachyarrhythmias and embolic stroke in a variety of clinical settings. Advanced IAB is a cause of left atrial electromechanical dysfunction and left atrioventricular dyssynchrony and has been associated with left ventricular diastolic dysfunction. P wave duration is associated with cardiovascular and all-cause mortality in the general population. Atrial conduction abnormalities should be identified as markers of atrial remodeling, prognostic indicators, and, in the case of advanced IAB, a true arrhythmologic syndrome. IAB and other P wave abnormalities should prompt the search for associated conditions, the treatment of which may partially reverse atrial remodeling or prevent it if administered upstream. Future studies will help define the role of preventive therapeutic interventions in high-risk patients, including antiarrhythmic drug therapy and oral anticoagulation. Implications for the treatment of heart failure and for pacing should also be further investigated.

Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The objective of the study is to demonstrate a common etiology of hyperkalemia and illustrate a potential iatrogenic errors in treatment.

Introduction: Conduction block in the posterior right atrium (RA) plays an important role in perpetuating atrial flutter (AFL). Although conduction blocks have functional properties, it is not clear how the block line changes with the pacing rate, pacing site, and administration of antiarrhythmic drugs., Methods and Results: Forty patients with typical AFL were enrolled. Pacing (110, 170, 230 ppm) from the coronary sinus ostium (CSo) and low lateral RA was performed. After 1 mg/kg pilsicainide (pure sodium channel blockade) administration, the pacing protocol was repeated. Conduction block was assessed based on a color-coded isopotential map and 20 points of virtual unipolar electrograms in the posterior RA using noncontact mapping. Block line proportion was defined as the percentage of length of the block line between the superior and inferior vena cava. The pacing rate-dependent extension of the block proportion was significant during pacing from both sides (pacing from the CSo: 59 ± 17% at 110 ppm, 69 ± 16% at 230 ppm, P < 0.05; pacing from the low lateral RA: 43 ± 19% at 110 ppm, 55 ± 22% at 230 ppm, P < 0.05). The block line was significantly longer during CSo pacing than during low lateral RA pacing at each rate (all P < 0.05). After pilsicainide administration, the block line extended further., Conclusion: In addition to pacing rate-dependent and site-dependent changes in the block line, pilsicainide further extended the block line length. This phenomenon explains the clinical observation that counterclockwise AFL occurs more frequently than clockwise AFL, and the mechanism of class IC AFL., (© 2012 Wiley Periodicals, Inc.)

Electropharmacological effects of chronically administered amiodarone and candesartan on atria that had been remodeled against congestive heart failure were assessed using dogs (about 10 kg in weight) with chronic atrioventricular block. Amiodarone was administered orally in a dose of 200 mg/body per day for the initial 7 days followed by 100 mg for the following 21 days (n = 7). Candesartan was administered in a dose of 12 mg/body per day for 28 days (n = 7). All animals survived the 4-week experimental period, indicating the lack of risks for inducing cardiohemodynamic collapse or torsade de pointes by these drugs. The plasma amiodarone concentration was 353 ng/ml at 4 weeks of treatment. Before candesartan treatment (control), intravenous administration of 30 ng/kg of angiotensin II increased the mean blood pressure by 18 mmHg, which was significantly decreased to 1 mmHg by 4 weeks of treatment. Amiodarone prolonged the atrial effective refractory period without affecting inter-atrial conduction time and decreased the duration of the burst pacing-induced atrial fibrillation, whereas candesartan hardly affected these variables. These results indicate that amiodarone should become a pragmatic pharmacological strategy against atrial fibrillation in patients with chronically compensated heart failure and suggest that a much higher dose of candesartan may be needed to exert its efficacy in this model.

We report the case of a patient in whom radiofrequency catheter ablation of the AV node was initially successfully performed for persistent atrial fibrillation with fast ventricular rate, but in whom atrioventricular conduction transiently resumes following therapy with levosimendan. Plausible hypothesis are discussed as well as potential implications.

Objectives: We sought to identify the triggers of ventricular tachyarrhythmia (VTA) in experimental models of long QT type 2 (LQT2) and long QT type 3 (LQT3) syndromes., Background: Most adverse cardiac events occurring in the long QT type 1 syndrome are related to sympathetic nerve activity. In contrast, various factors may trigger VTA in patients with LQT2 and LQT3., Methods: The mode of onset of VTA and therapeutic effects of the potassium-adenosine triphosphate channel opener nicorandil were compared in canine models of LQT2 and LQT3, using three induction protocols: 1) bradycardia produced by atrioventricular block (BRADY); 2) programmed ventricular stimulation; and 3) electrical stimulation of the left stellate ganglion (left stellate stimulation [LSS]). Transmural unipolar electrograms were recorded, and the activation-recovery interval (ARI) was measured., Results: Ventricular tachyarrhythmias developed during BRADY in all six experiments in the LQT3 model, but in none of the six experiments in LQT2. Programmed ventricular stimulation induced VTA in two experiments of the LQT2 model, but in none of the LQT3 experiments. Stimulation of the left stellate ganglion induced VTA in three experiments in LQT2 and in two experiments in LQT3. Nicorandil caused greater shortening of ARI and greater attenuation of transmural ARI dispersion in the LQT2 model than in the LQT3 model. After treatment with nicorandil, a single VTA was induced in the LQT2 model by LSS, whereas in the LQT3 model, VTA remained inducible by BRADY in four experiments and LSS in one experiment., Conclusions: An abrupt increase in sympathetic activity appeared arrhythmogenic in both models. Nicorandil attenuated the heterogeneity of ventricular repolarization and suppressed the induction of VTA in the LQT2 model, but had a limited therapeutic effect in the LQT3 model.

Amiodarone effectively blocks both the sodium and calcium channels and beta-adrenoceptors, in addition to blocking several potassium currents including IKr, IKs, Ito, IK1, IKACh and IKNa. The incidence of clinical torsade de pointes (TdP) associated with amiodarone has been reported to be low and the present study compared the proarrhythmic potential of amiodarone with that of a selective IKr channel blocker, sematilide, using a canine chronic atrioventrucular block model. Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered orally without anesthesia under continuous ECG monitoring. Both drugs prolonged the QT interval, although the onset was faster for sematilide. The high dose of sematilide induced TdP in 3 of 4 animals, which caused their death, but neither the low dose of sematilide nor the 2 dosages of amiodarone induced lethal ventricular arrhythmias. These results suggest that IKr channel inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP.

Background: Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP). The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment., Methods and Results: Amiodarone (n=7, 40 mg. kg(-1). d(-1)) and dronedarone (n=8, 20 mg/kg BID) were started at 6 weeks of CAVB (baseline). Six dogs served as controls. Surface ECGs and endocardially placed monophasic action potential catheters in the left (LV) and right (RV) ventricles were recorded to assess QTc time, action potential duration (APD), interventricular dispersion (DeltaAPD=LV APD minus RV APD), early afterdepolarizations (EADs), ectopic beats, and TdP. Both amiodarone (+21%) and dronedarone (+31%) increased QTc time. Amiodarone showed no increase in DeltaAPD in 4 of 7 dogs, whereas dronedarone augmented DeltaAPD in 7 of 8 animals. After dronedarone, TdP occurred in 4 of 8 dogs with the highest DeltaAPD (105+/-20 ms). TdP was never seen with amiodarone, not even in the dogs that had DeltaAPD values comparable to those with dronedarone. Furthermore, a difference existed in EADs and ectopic activity incidence (dronedarone 3 of 8; amiodarone 0 of 7), which was also seen during an epinephrine challenge., Conclusions: In the CAVB dog model, both amiodarone and dronedarone prolong QT time (class III effect). The absence of TdP with amiodarone seems to be related to homogeneous APD lengthening in the majority of dogs and the lack of EADs and/or ventricular ectopic beats in all.

The purpose of this study was to investigate the therapeutic response to atropine of patients experiencing hemodynamically compromising bradyarrhythmia related to acute myocardial infarction (AMI) in the prehospital (PH) setting and the therapeutic impact of the PH response to atropine on further Emergency Department (ED) care. In addition, the prevalence of AMI in patients presenting with atrioventricular block (AVB) is noted. Retrospective review of PH, emergency department (ED), and hospital records. PH patients, with hemodynamically compromising bradycardia or AVB with evidence of spontaneous circulation, who received atropine as delivered by emergency medical services (EMS) personnel, were used. Urban/suburban fire department-based emergency medical services (EMS) system with on-line medical control serving a population of approximately 1.6 million persons. Hemodynamic instability was defined as the presence of any of the following: ischemic chest pain, dyspnea, syncope, altered mental status, and systolic blood pressure less than 90 mm Hg. Bradycardia was defined as sinus bradycardia, junctional bradycardia, or idioventricular bradycardia (grouped as bradycardia), whereas AVB included first-, second- (types I and II), or third-degree (grouped as AVB). The response that occurred within 1 minute of atropine dosing was recorded as none, partial, complete, or adverse. Comparisons were made between patients with AMI and non-AMI hospital discharge diagnoses. The diagnosis of AMI was confirmed by abnormal elevations in creatinine phosphokinase MB fraction. One hundred seventy-two patients meeting entry criteria were identified. Of these, 131 (76.1%) had complete PH, ED, and hospital records and were used for data analysis. Forty-five patients (34.3%) had a primary hospital discharge diagnosis of AMI; the remaining patients had a non-AMI discharge diagnosis. AMI patients were significantly younger (67 +/- 12 v 73 +/- 13 years, P = .025), were less likely to have a history of heart disease (35.5% v54.7%, P = .038), and were more likely to present with chest pain (68.9% v24.4%, P < .001) or hypotension (60% v37.2%, P = .013) compared with non-AMI patients. Forty-five of 131 patients presented with AVB, of which 25 had a hospital discharge diagnosis of AMI (55.6%). The mean time from first dose of atropine to ED arrival and the total dose of atropine received in the PH setting did not differ between AMI and non-AMI groups (15.2 +/- 7.7 v 16.2 +/- 8.7 minutes, P= .5; and 0.9 +/- 0.49 v 1.0 +/- 0.58 mg, P = .25). The likelihood of achieving normal sinus rhythm in the PH setting did not differ between AMI and non-AMI groups (40% v 18.6%, P = .07). No differences were found between AMI and non-AMI groups in the amount of additional atropine given (1.2 +/- 0.58 v 1.3 +/- 1.1 mg, P = .58) or the use of other resuscitative therapies after ED arrival (isoproterenol, 13.3% v12.8%, P = .93; dopamine, 28.9% v26.7% P = .79; transcutaneous pacing, 26.7% v26.7%, P = .99; transvenous pacing, 8.9% v5.8%, P = .51), with the exception of thrombolytic therapy (24.4% v 0%, P< .001) and cardiac catheterization (22.2% v3.4%, P = .001). Despite a lack of significant difference in achieving a normal sinus rhythm in the prehospital or ED setting, AMI patients were more likely to achieve a normal sinus rhythm over the total course of PH and ED care than non-AMI patients (44.4% v24.4%, P = .019). Hemodynamically unstable (by ACLS criterion) AVB presenting in the PH setting is associated with a hospital diagnosis of AMI in most (55.6%) patients in this study. AMI patients with hemodynamically unstable AVB or bradycardia are no more likely to respond to atropine therapy in the PH setting than patients with non-AMI hospital diagnoses. Finally, although there is no difference in the treatment of compromising AVB or bradycardia received by AMI versus non-AMI patients in the PH or ED setting, AMI patients are more likely to achieve a normal sinus rhythm over the t

Amiodarone is useful for the treatment of ventricular and supraventricular arrhythmias, but it has been associated with several adverse effects. Amiodarone-induced hepatotoxicity is a frequent complication and often consist in a mild and asymptomatic elevation of liver function tests, although severe cases have been described. A case of severe amiodarone-induced hepatotoxicity slowly resolving after discontinuation of the drug and in which liver biopsy was crucial for diagnosis is reported. Although there are no pathognomonic histopathological findings, phospholipidosis is the morphologic hallmark of amiodarone hepatotoxicity.

Background: Recent molecular biological investigations have identified abnormal genes in familial forms of long QT syndrome, but in bradycardia dependent acquired long QT syndrome, no such genetic abnormality has yet been identified., Objective: To investigate the relation between the responses of QT interval to pacing change and to disopyramide., Methods: This study included 13 patients with bradyarrhythmia who had undergone pacemaker implantation. The patients were divided into two groups: group I (n = 8), patients with QT prolongation (QT interval > or = 500 ms) during bradycardia; group II (n = 5), patients without QT prolongation (QT interval < 500 ms) during bradycardia. The responses of QT interval caused by the change of pacing rate were determined and compared with the changes of the QT interval after disopyramide administration., Results: The QT interval in group I was significantly longer than that in group II when the pacing rate was decreased from 110 to 50 beats/min: mean (SD) 451 (16) v 416 (17) ms at 90 beats/min (p = 0.0033), and 490 (19) v 432 (18) ms at 70 beats/min (p = 0.0002), respectively. The QT interval was prolonged significantly by disopyramide in both groups, but the change was more pronounced in group I than in group II: 78 (33) v 35 (10) ms (p < 0.05)., Conclusions: This study suggests that the patients showing bradycardia dependent QT prolongation are also more markedly affected by disopyramide and that abnormal potassium channel may be the underlying mechanism.

Ipratropiumbromid is used in adults for a variety of bradyarrhythmias. In contrast this therapy has not yet been established in childhood, where symptomatic bradyeardias are less frequent. Since Ipratropiumbromid has less side effects (especially concerning the central nervous system) and a longer half time than atropin, we investigated the efficacy of Ipratropiumbromid in 12 children (mean age 7.2 yrs.) in the course of 2 1/2 years. We found a significant increase of the minimal and mean heart rate in Holter-Eeg-recordings. Only in 7 of 12 patients we obtained a sufficient therapeutic effect. In one patient we had to terminate the therapy because of side effects. In two patients with atrioventricular block and two children with higher degree sinus node dysfunction could be removed only by implantation of a pacemaker. In another case we observed the proarrhythmical effect of Ipratropiumbromid. Summarizing we think, that the therapy with Ipratropiumbromid may be useful in symptomatical supranodal bradyarrhythmias in childhood in regard of side effects.

To assess the efficacy and safety of current pharmacologic therapy for supraventricular tachycardia (SVT) in infants, we reviewed 112 infants treated between July 1985 and March 1993. The SVT mechanism was determined by esophageal electrophysiologic study and involved an accessory pathway in 86, atrioventricular (AV) node reentry in 10, atrial muscle reentry in 11, and an ectopic atrial tachycardia in 5 patients. Of six infants not treated, none had clinical recurrences of SVT. Of the 106 patients treated, 70% remained free of tachycardia while receiving digoxin, propranolol, or both. Class I antiarrhythmic agents were necessary for 13 patients, and class III agents were required for another 13 infants. Verapamil was used in one infant with AV node reentry tachycardia. Nine infants with complex clinical presentations were believed to have failed medical management and underwent radiofrequency ablation. Five patients died, four of complications related to structural heart disease and one shortly after radiofrequency ablation was performed. No deaths appeared to be related to antiarrhythmic medications. No drug-related side effects requiring medication change occurred, and no proarrhythmia was observed. Thus medical therapy appears to be effective and safe in infants with SVT. Radiofrequency ablation should be reserved for rare infants who fail aggressive medical regimens or when the situation is complicated by ventricular dysfunction, severe symptoms, or complex congenital heart disease.

We have assessed the ability of the new amiodarone-like antiarrhythmic agent, SR 33589, to reduce the incidence of ischemia- and reperfusion-induced arrhythmias, in comparison to amiodarone, D-sotalol, and lignocaine. Rats were anesthetized, artificially ventilated, and the thorax opened by a left thoracotomy. Ischemia was induced by left coronary artery ligation, and reperfusion was achieved (after a 5-min period of ischemia) in a separate group of rats by removing the ligature. Agents were given intravenously 5 min before occlusion or orally 4 h before study. During a 20-min period of ischemia, SR 33589 reduced significantly the incidence of ventricular fibrillation (VF) from 80 to 30% (p < 0.05) at 3 mg/kg i.v. and eliminated VF and mortality at 10 mg/kg i.v. In contrast, amiodarone at 10 mg/kg i.v. reduced significantly only the incidence of mortality during ischemia (from 60 to 0%, p < 0.01), while having no significant effect on 3 mg/kg i.v. On reperfusion (after a 5-min period of ischemia), SR 33589 reduced significantly the incidence of mortality (from 90 to 20%, p < 0.01) at 1 mg/kg and eliminated VF and mortality when administered at 3 and 10 mg/kg. Against both ischemia- and reperfusion-induced arrhythmias, approximately 20% of animals showed AV block at the highest dose of SR 33589 tested. This was not observed with lower doses. Amiodarone (10 mg/kg i.v.) eliminated completely reperfusion-induced VF and mortality while having no significant effect at 1 and 3 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac dysfunction is often manifested as arrhythmia, with disruption of the normal periodicity and regularity of electromechanical activity. The therapy for arrhythmia begins with proper diagnosis, since many pharmacological interventions are themselves arrhythmogenic. Intervention for acute arrhythmia involves correction of underlying systemic conditions by ensuring adequate oxygenation, ventilation, acid-base homeostasis, electrolyte balance, and fluid status. Classification of antiarrhythmic agents assists in a structured treatment approach that utilizes different agents based on the etiology of the arrhythmia and the drug's mechanism of action. A deliberate treatment strategy guided by the morphological criteria of the arrhythmia modified by the rate and duration of complexes, noting symptoms and hemodynamic stability, is desirable.

Introduction: The hypothesis that levcromakalim, a potassium channel (IK-ATP) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs., Methods and Results: A low dose of levcromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (1) d-sotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs), (2) sustained ouabain-induced VTs, which are dependent on delayed afterdepolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 +/- 515 to 1700 +/- 610 msec (P < 0.05), remained similar after levcromakalim (1655 +/- 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 +/- 55 to 550 +/- 40 msec (P < 0.05), normalized to 405 +/- 70 msec (P < 0.05). Levcromakalim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 +/- 35 to 290 +/- 35 msec (P < 0.05). Pretreatment with a beta blocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction., Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.

Antiarrhythmic agents alter cardiac conduction, refractoriness, and action potential duration in a rate dependent fashion. A simple in vivo model was developed to measure these variables over a wide range of cycle lengths. Complete heart block was produced in dogs using an 8 French hexapolar ablation catheter, anterior skin electrode, and radiofrequency current (30 W, 13.6 +/- 2.6 seconds). Ventricular pacing and monophasic action potential recordings were performed using a single combination catheter. QRS and action potential durations were measured at multiple cycle lengths and after an abrupt change in paced cycle length. Ventricular effective refractory periods were also measured at multiple cycle lengths. Data obtained during flecainide and d-Sotalol infusions are presented. This simple model allows detailed in vivo evaluation of the electrophysiological effects of antiarrhythmic agents and combinations.

In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block.

In this study involving 45 patients with the normal function of the sinus node and 10 patients showing signs of its damage (n-10), intravenous administration of ethmozine in a dose of 150 mg (1.5-2 mg/kg) exerted atropine like action. In four cases with dysfunction of the sinus node the drug significantly increased the time of the restoration of sinus node function. Ethmozine induced a Stage II sinoatrial block in 3 out of 10 patients with sinus node dysfunction. The above data suggest that ethmozine produces an atropine-like effect on the sinus node. In some patients with sinus node dysfunction, ethmozine may impair the function of the sinus node which calls for caution while employing the drug in such cases. The inhibitory effect of the agent on the sinoatrial conduction in the patients studied suggests that ethmozine may prove an effective antiarrhythmic drug for treating patients with paroxysmal sinoatrial tachycardia.

The atrioventricular block was produced in dogs 24 hours after the occlusion of the left descending coronary artery by formalin injection into the atrioventricular node or the bundle of His. The intensity and duration of the ectopic foci inhibition produced by ethmozine and by its diethylamine analogue (ethmozine DAA) were compared. It was shown that intravenous infusion of 3 mg/kg ethmozine reduced the frequency of the ectopic ventricular excitations by 28% (n = 6), 0.5 mg/kg ethmozine DAA - by 46% (n = 7), and 1 mg/kg ethmozine DAA - by 78% (n = 8). In 50% of the animals 1 mg/kg ethmozine DAA completely suppressed the ectopic activity. Duration of the drugs action was determined by the time necessary for the attainment of 50% of the maximal effect in the inhibition of ectopic exitation frequency (for 3 mg/kg ethmozine it was 32.7 +/- 2.5 min, for 0.5 mg/kg ethmozine DAA - 5.1 +/- 7.2 min, and for 1 mg/kg ethomozine DAA - 55.0 +/- 9.8 min). The results obtained suggest that the ethmozine DAA action is more intensive and of longer duration than ethmozine, and effective at the late stage of experimental myocardial infarction.

Patients with advanced interatrial conduction block with retrograde activation to the left atrium present a high incidence of supraventricular tachyarrhythmias. We report the value of preventive antiarrhythmic treatment in these patients.

In vitro experiments have shown that the antiarrhythmic effects of propafenone are due to a direct depressant action and to a beta-blocking activity. In this study a method was used to evaluate the direct effect and the autonomically mediated actions of an antiarrhythmic agent in a clinical setting. An electrophysiological study was performed twice, at an interval of 24 hr, in 17 patients (age: 52 +/- 17 years) with normal resting and intrinsic heart rate. In the first study the overall effect of intravenous propafenone (1.5-2 mg/kg) was evaluated by comparing the sinus node parameters obtained during the basal state and after drug administration. In the second study the direct depressant effect of the drug was evaluated by comparing the electrophysiological variables obtained following autonomic blockade (propranolol 0.2 mg/kg and atropine 0.04 mg/kg) and after propafenone. In the first study there was no significant change in the sinus cycle length and corrected sinus node recovery time and only a small (9.1%) increase in sinuatrial conduction time, whereas in the second study these variables increased significantly. The degree of increase in sinus cycle length and corrected sinus node recovery time was significantly higher in the second study than in the first one. These data suggest that: (1) propafenone has direct depressant effect on sinus automaticity but this effect is counteracted by autonomically mediated actions (most likely of vagolytic type); (2) the beta-blocking effect of the drug demonstrated in isolated atria is not seen in a clinical setting.

Guidelines for a step-wise plan of treatment of tachycardias have been compiled based on clinical empirical experience and with the aid of surface electrocardiograms, intracardial electrograms and stimulation techniques. The plan is primarily with the aid of surface electrocardiograms, intracardial electrograms and stimulation techniques. The plan is primarily oriented with respect to the antiarrhythmic efficacy, the adverse reactions and the practicability of the respective agents. Any type of tachycardia, including premature atrial or ventricular contractions, may be regarded as indication for treatment. Treatment is not indicated only in those asymptomatic patients with rare and evanescent tachycardias and in those with less than 300 premature contractions per hour. Beta-adrenergic blockers are the drugs of choice for the persistent sinus tachycardia. Should the latter agents be contraindicated, propafenon, amiodarone or aprindine may be administered. Verapamil and/or digitalis are indicated only for suppression of paroxysmal sinus tachycardias. Atrial premature contractions are best managed with guinidine or disopyramid. An acute reduction of rapid ventricular rates associated with atrial tachycardias, atrial flutter or fibrillation can best be attained through the administration of verapamil prior to digitalis or beta-adrenergic blockers. Re-establishment of sinus rhythm and prophylactic suppression of the latter should be undertaken with quinidine or disopyramid in combination with digitalis and/or either a beta-adrenergic blocker or intravenously-administered verapamil. Verapamil is the drug of choice for initial management of AV-junctional tachycardia for which a combination with digitalis may be considered. An alternative combination is that of a beta-adrenergic blocker and digitalis. For the acute treatment of ventricular tachycardias, lidocain has proved most effective. Although ajmaline and/or propafenon may be given should no response be obtained, electrical cardioversion would be more appropriate. To prevent ventricular tachycardia or when treatment is indicated for ventricular premature beats, ajmaline, propafenon, quinidine, disopyramid or mexiletine, occasionally in combination with a beta-adrenergic blocker should be employed. Verapamil and/or ajmaline, are usually very effective for termination of reciprocal tachycardias. Ajmaline or propafenon in combination with a beta-adrenergic blocker is recommended for the prophylactic treatment of reciprocal tachycardia. In patients who additionally have bradycardia, prolonged QT-intervals or pre-excitation syndromes, the guidelines should be modified accordingly.

The course of a 20-year-old patient with head injury and fractures of the ribs is reported, in whom sinus tachycardia has now persisted for three years. Antiarrhythmic treatment with calcium antagonists, beta-blocking agents and digitalis did not reduce the rate of the tachycardia. Contusio cordis, as well as different mechanisms of arrhythmias after cerebral trauma are discussed.

The influence of Mexiletine on the av-conduction time and sinus node recovery time of 24 patients with and without disturbance of impulse formation and conduction was examined. There was no change of conduction time proximal to the His-bundle. Four patients developed block distal to the His-bundle, 3 of which had a conduction disturbance before application of the drug consisting in 2:1 av-block or bifascicular block. Two patients with WPW-syndrome showed no change of impulse conduction. Five out of 12 patients showed an increase of the effective recovery period. Three out of 15 patients showed an increase of threshold potential from 0.35 to 0.7 volt with suppression of escape rhythm. The sinus node recovery time was prolonged in 2 out of 9 patients, one of which had a sick sinus syndrome. As there seems to be some influence of Mexiletine on sinus node impulse formation and the impulse conduction distal to the His-bundle, this drug probably should be used with caution in patients with disturbance of automaticity and distal av-conduction.

The knowledge of various dysrhythmias and their prognostic value permits the selection of appropriate diagnostic and management strategies. The most frequent pediatric dysrhythmias are described: premature atrial and ventricular contractions, supraventricular tachycardias, preexcitation syndrome, long Q-T syndrome, sick sinus syndrome, A-V blocks congenital and acquired. These arrhythmias may be related to structural abnormalities of the conduction system or may reflect temporary cardiac immaturity, as in the newborn, or may occur after surgical repair of a congenital cardiac lesion. It is important decide if the arrhythmias is benign and likely to resolve spontaneously or if it is potentially dangerous. Sometimes an arrhythmias indicates underlying extracardiac disease such as central nervous system disease, sepsis, hypoglycemia, drug toxicity, severe tissue hypoxia, electrolyte abnormalities. In these instances the treatment of the underlying cause will correct the rhythm abnormalities.

Arrhythmias are the expression of disordered stimulus formation or conduction. Focal genesis is due to an abnormal automatism in primary, secondary and tertiary impulse centers. Conduction blockade leads to bradycardial substitute rhythms which are determined by the site of the lesion. Bradycardial arrhythmias with a high degree of risk, with disturbed impulse automatism or with impaired hemodynamics require treatment with a pacemaker. Tachycardial and extrasystolic arrhythmias are treated today according to the differential therapeutic aspects. Treatment is also obligatory for premonitory arrhythmias and an identified Stokes-Adams disease. Ventricular fibrillations, high-grade ventricular bradycardia and asystole are cardiological emergencies.