[Therapy of atrial fibrillation in the critically ill]. / Therapie des Vorhofflimmern beim kritisch Kranken.

Atrial fibrillation (AF) is the most common form of arrhythmia in the intensive care unit (ICU) and is associated with increased mortality. A total of five types of AF can be distinguished: initially diagnosed, paroxysmal, persistent, long-standing persistent and permanent AF. In addition to the initial treatment, antithrombotic therapy, rate and rhythm management can be used. The treatment of comorbidities is part of the patient management and for patients with increased risk of thromboembolic events anticoagulation is recommended. The simplest risk assessment scheme is the CHADS score. In the acute setting rate control is important. Direct current cardioversion is urgently recommended for patients with AF when hemodynamic instability is present even in patients with AF and pre-excitation in Wolff-Parkinson-White syndrome. Pharmacological cardioversion may be considered in patients with AF when hemodynamic stability is present. When choosing the antiarrhythmic agent for critically ill patients only amiodarone can be considered with some exceptions due to the specific contraindications.

Dronedarone prevents microcirculatory abnormalities in the left ventricle during atrial tachypacing in pigs.

BACKGROUND AND PURPOSE: Atrial fibrillation induces ischaemic microcirculatory flow abnormalities in the ventricle, contributing to the risk for acute coronary syndromes. We evaluated the effect of dronedarone on ventricular perfusion during rapid atrial pacing (RAP). EXPERIMENTAL APPROACH: Coronary and fractional flow reserve (CFR/FFR) were measured in the left anterior descending artery in 29 pigs. Six received RAP, six received RAP with dronedarone (RAP/D), seven received dronedarone alone, four received RAP with amiodarone (RAP/A), and six received neither (sham). In ventricular tissue, oxidative stress/ischaemia-related gene and protein expression was evaluated by RT-PCR and Western blotting; Isoprostanes were measured by GC-MS procedures. KEY RESULTS: CFR was decreased in the RAP group, compared with other groups. FFR was not different between groups. Effective refractory period was reduced in RAP compared with RAP/D. RAP-activated PKC phosphorylation tended to be decreased by dronedarone (P= 0.055) RAP induced NOX-1 and NOX-2 protein and the mRNA for hypoxia-inducible factor-1α (HIF-1α). Dronedarone reduced the pacing-dependent increase in the expression of NOX-2 protein and of HIF-1α mRNA. The oxidative stress marker, F(2)-isoprostane, was increased by RAP and this increase was attenuated by dronedarone. Other oxidative stress/ischaemia-related genes were induced by RAP compared with sham and were decreased by dronedarone treatment. In HL1 cells, dronedarone significantly inhibited the increased phosphorylation of PKCα after oxidative stress, with an almost significant effect (P= 0.059) on that after RAP. CONCLUSIONS AND IMPLICATIONS: Dronedarone abolished RAP-induced ventricular microcirculatory abnormalities by decreasing oxidative stress/ischaemia-related gene and protein expression in the ventricle.

[New antiarrhythmic drugs for therapy of atrial fibrillation: II. Non-ion channel blockers]. / Neue Antiarrhythmika in der Therapie des Vorhofflimmerns--II. Nicht-Ionenkanalblocker.

The therapeutic approach to atrial fibrillation is difficult and challenging. The effect of "classical" antiarrhythmic agents is based on their inhibitory effects on various ion channels. However, therapeutic benefit of these agents is often limited. The primary goal of this article is to discuss new therapeutic approaches using non-ion channel blocking drugs in the treatment of atrial fibrillation. Some of the substances discussed in this article have been used already in the clinical practice. Others, for example gentherapeutic approaches, are still in the experimental state. In contrast to ion channel blocking agents their efficacy is based on the suppression of structural remodeling. Hence, it can be assumed that due to these effects they may also be beneficial in the primary prevention of atrial fibrillation.