Mechanisms of action of atrial-specific anti-arrhythmic drugs

Atrial fibrillation (AF) is a rhythm disorder characterized by fast and irregular activations of the atria. The patients with AF have an increased risk for having a stroke and for developing other cardiovascular diseases. Having effective strategies for treatment of AF is therefore essential. None of the currently available therapeutic strategies for treatment of AF achieves satisfying success rates. Moreover, the use of anti-arrhythmic drugs (AADs, drugs that can terminate the arrhythmia) is limited by their side effects, especially by an increased risk for development of ventricular arrhythmias. This creates an urgent need for development of new AADs that would be safe and efficient at the same time, as well as for better understanding of the mechanisms that are responsible for maintenance and termination of AF. The thesis describes antiarrhythmic mechanisms of two novel AADs in goats with AF. Both drugs are atrial-selective, which means that they affect atria but not ventricles. The results suggest that these drugs have a potential to become safe and efficient strategies for treatment of AF. The thesis also provides new insights into the mechanisms underlying AF termination. It demonstrates that regardless of the presence or the type of AAD, cardioversion of AF in goats is associated with increased organization of the fibrillatory process and with abrupt changes in electrophysiological parameters. Finally, the thesis presents a novel method for processing of experimental data that were acquired by a technique called optical mapping. Applying this method, the thesis provides new insights into the mechanisms underlying perpetuation of the arrhythmia