Moderne Pharmakotherapie bei supraventrikulären und ventrikulären Herzrhythmusstörungen

Currently the pharmacological approach still represents the mainstay in the acute phase of arrhythmia management as well as in the chronic treatment phase of specific entities such as atrial fibrillation. However, non-pharmacological options have recently emerged as frequently used first-line tools for the treatment of various supraventricular and ventricular heart rhythm disturbances. Nevertheless, antiarrhythmic drug treatment is frequently used as a bridging or adjunctive therapy in conjunction with catheter ablation or implantable cardioverter defibrillators. Antiarrhythmic agents constitute a very heterogeneous group prone to various drug interactions and side-effects. Therefore, this article aims to summarise the most important facts and recent findings with regard to appropriate contemporary pharmacological therapy of atrial and ventricular arrhythmias in clinical practice.     

Catheter ablation of common-type atrial flutter guided by three-dimensional right atrial geometry reconstruction and catheter tracking using cutaneous patches: a randomized prospective study

INTRODUCTION: EnSite NavX (NavX) is a novel mapping and navigation system that allows visualization of conventional catheters for diagnostic and ablative purposes and uses them to create a three-dimensional (3D) geometry of the heart. NavX is particularly suitable for ablation procedures utilizing an anatomic approach, as in the setting of common-type atrial flutter (AFL). The aim of this study was to compare NavX-guided and conventional ablation procedures for AFL. METHODS AND RESULTS: Forty consecutive patients (32 male, 59 +/- 12 years) with documented AFL were randomized to undergo fluoroscopy-guided (group I, 20 patients) or NavX-guided (group II, 20 patients) ablation, including 3D isthmus reconstruction. The same catheter setup was used in both groups. The endpoint of bidirectional isthmus block was obtained in all patients. Compared to conventional approaches, NavX-guided procedures significantly reduced fluoroscopy time (5.1 +/- 1.4 min vs 20 +/- 11 min, P < 0.01) and total x-ray exposure (5.1 +/- 3.1 Gycm2 vs 24.9 +/- 1.6 Gycm2, P < 0.01). Isthmus geometry reconstruction could be performed in all patients of group II. In 4 patients (20%) of group II, anatomic isthmus variations were detected by NavX. No significant differences in radiofrequency current applications and procedural times were found between the two groups. CONCLUSION: NavX technology allows geometry reconstruction of the cavotricuspid isthmus. NavX-guided ablation of AFL reduces total x-ray exposure compared to the fluoroscopy-guided approach but does not prolong procedure time.     

High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation

BACKGROUND: Areas of complex fractionated atrial electrograms (CFAEs) have been implicated in the atrial substrate of atrial fibrillation (AF). The mechanisms underlying CFAE in humans are not well investigated. OBJECTIVES: The purpose of this study was to investigate the regional activation pattern associated with CFAE using a high-density contact mapping catheter. METHODS: Twenty patients with paroxysmal AF were mapped using a high-density multielectrode catheter. CFAE were mapped at 10 different sites (left atrium [LA]: inferior, posterior, roof, septum, anterior, lateral; right atrium [RA]: anterior, lateral, posterior, septum). Local atrial fibrillation cycle length (AFCL) was measured immediately before and after the occurrence of CFAE, and the longest electrogram duration (CFAEmax) was assessed. RESULTS: Longer electrogram durations were recorded in the LA compared with the RA (CFAEmax 118 +/- 21 ms vs 104 +/- 23 ms, P = .001). AFCL significantly shortened before the occurrence of CFAEmax compared with baseline (LA: 174 +/- 32 ms vs 186 +/- 32 ms, P = .0001; RA: 177 +/- 31 ms vs 188 +/- 31 ms, P = .0001) and returned to baseline afterwards. AFCL shortened by >or=10 ms in 91% of mapped sites. Two different local activation patterns were associated with occurrence of CFAEmax: a nearly simultaneous activation in all spines in 84% indicating passive activation, and a nonsimultaneous activation sequence suggesting local complex activation or reentry. CONCLUSION: Fractionated atrial electrograms during AF demonstrate dynamic changes that are dependent on regional AFCL. Shortening of AFCL precedes the development of CFAE; thus, cycle length is a major determinant of fractionation during AF. High-density mapping in AF may help to differentiate passive activation of CFAE from CFAE associated with an active component of the AF process.     

Large Tip Electrodes for Successful Elimination of Atrial Flutter Resistant to Conventional Catheter Ablation

The most widely accepted criterion for successful radiofrequency catheter (RFC) ablation of typical atrial flutter is the development of bi-directional isthmus block. In a subset of patients, conventional RFC ablation fails to achieve this endpoint because deeper and wider lesions are required. We investigated the efficacy of a long 8-mm tip catheter in these cases.One hundred and seventy-four consecutive patients (137 male; 61 ± 9 years) with recurrent typical atrial flutter underwent conventional RFC ablation first with a standard 4 mm tip catheter. In resistant cases (n = 52), ablation was continued using a large tip 8-mm catheter when the 4-mm tip catheter failed. Resistant atrial flutter was identified when 21 RFC pulses failed to reach the selected endpoint of bi-directional isthmus block or in cases of transient bi- directional block (at least 3 episodes).In 122 of the 174 patients (70%) conventional atrial flutter ablation was successfully performed with 13 ± 5 RFC applications. In the remaining 52 subjects (30%), the ablation procedure was completed using the large tip electrode catheter. In 30 of these 52 patients (58%), the catheter was changed because of persistent intra-atrial conduction after 21 RFC pulses and in 22 (42%) because of intermittent conduction block after 11 ± 5 applications. Using the large tip electrode catheter, the selected endpoint was achieved in all patients of both groups with 3 ± 2 RFC pulses (power output of 50–60 W, pulse duration of 60 sec). No post-procedure complications were observed. After 15 ± 5 months of follow-up, 16 patients (9%) had recurrence of atrial flutter. Five of the patients had been in the resistant group. In patients with atrial flutter resistant to conventional ablation therapy, the long tip (8-mm) catheter appears to be a safe and effective alternative to use of the conventional 4-mm tip catheter.     

Die Wirkung von Fols?ureantagonisten (Methotrexat) auf die Regeneration der Darmschleimhaut

Zusammenfassung In vergleichenden Untersuchungen wird die Wirkung der folsÄureantagonistisch wirksamen Substanz Methotrexat auf die Regeneration der Schleimhaut von Duodenum, Jejunum, Ileum, Colon ascendens und Colon descendens von MÄusen geprüft.Im Langzeitversuch findet sich eine bis zu 3 Wochen fortschreitende langsame Zottenatrophie, vor allem am Duodenum, die auf einen Zellverlust in der Population der Regenerationszone zurückzuführen ist.Bei einmaliger hochdosierter Zufuhr von Methotrexat (Stoversuch) wird die Regenerationszone geschÄdigt, wobei anfangs der Verlust regenerationsfÄhiger Zellen mit einer gesteigerten DNS-Synthese der Restpopulation beantwortet wird; über eine gesteigerte Zellneubildung ist nach 4 Tagen die Regenerationszone wieder weitgehend hergestellt. WÄhrend der Blockade der Regenerationszone ist die Auswanderung differenzierter Zellen auf die Zotten unterbrochen bzw. verzögert; nach Wiederherstellung findet sich ein beschleunigter Zellersatz. Entsprechend dem langsameren physiologischen Zellersatz am Colon ascendens und Colon descendens ist hier eine Methotrexatwirkung in Form einer vorüber gehenden Blockade nur in abgeschwÄchter Form feststellbar.

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The action of folic acid antagonists (methotrexate) on the regeneration of the intestinal mucosa

Summary Comparative studies were made of the action of Methotrexate, the folic acid antagonist, on the regeneration of the mucosa of the duodenum, jejunum, ileum, ascending and descending colon of the mouse. In chronic experiments an atrophy of villi slowly developed up to three weeks, especially in the duodenum. The atrophy was related to a loss of some of the cells of the regeneration zone. On administering a. single large dose of Methotrexate (push-experiment) the regeneration zone was damaged. Consequently, at the onset the loss of the cells capable of regenerating provoked an increased DNA synthesis of the remaining cells. After four days the regenerative zone was nearly restored by an increased renewal of cells. During the block of the regeneration zone, the migration of differentiated cells to the villi was interrupted or delayed. After restoration there was an accelerated renewal of cells. In the ascending and descending colon, where the physiological renewal of cells is slower than in other parts of the intestine, the effect of Methotrexate became apparent in a diminished form as a temporary block.

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Herrn Professor Dr. W.Büngeler zum 65. Geburtstag.

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Inaug.-Diss. München. Die Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.     

The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation

Retigabine (N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) has a broad anticonvulsant spectrum and is currently in clinical development for epilepsy. The compound has an opening effect on neuronal KCNQ channels. At higher concentrations an augmentation of gamma-aminobutyric acid (GABA) induced currents as well as a weak blocking effect on sodium and calcium currents were observed. The goal of this study was to characterise the activity of retigabine in models of acute and neuropathic pain and to investigate if the potassium channel opening effect of retigabine contributes to its activity.Retigabine was tested in mice and rats in the tail flick model of acute pain and in the nerve ligation model with tight ligation of the 5th spinal nerve (L5) using both thermal and tactile stimulation. While retigabine like gabapentin had almost no analgesic effect in mice it showed some analgesic effects in rats in the tail flick model. These effects could not be antagonised with linopirdine, a selective KCNQ potassium channel blocker, indicating a different mode of action for this activity. In L5-ligated rats retigabine significantly and dose-dependently elevated the pain threshold and prolonged the withdrawal latency after tactile and thermal stimulation, respectively. In the L5 ligation model with thermal stimulation retigabine 10 mg/kg p.o. was as effective as 100 mg/kg gabapentin or 10 mg/kg tramadol. The L5 model with tactile stimulation was used to test the role of the KCNQ potassium channel opening effect of retigabine. If retigabine 10 mg/kg p.o. was administered alone it was as effective as tramadol 10 mg/kg p.o. in elevating the pain threshold. Linopirdine (1 and 3 mg/kg i.p.) had nearly no influence on neuropathic pain response. If we administered both retigabine and linopirdine the effect of retigabine was abolished or diminished depending on the dose of linopirdine used.In summary, retigabine is effective in predictive models for neuropathic pain. The activity is comparable to tramadol and is present at lower doses compared with gabapentin. Since the anti-allodynic effect can be inhibited by linopirdine we can conclude that the potassium channel opening properties of retigabine are critically involved in its ability to reduce neuropathic pain response.