Atrial specific potassium channels as new drug targets in atrial fibrillation

Atrial fibrillation is the most common chronic arrhythmia afflicting 6% of the
population over the age of 60 years. With aging of our society, the prevalence
will even increase in the future. The socio-economic consequences of the
increasing incidence of the arrhythmia are manifold. AF is the most important
risk factor for stroke, it increases mortality and morbidity of patients with
cardiovascular diseases and strongly impairs quality of life. Restoration of
sinus rhythm is a primary goal in AF management but not often can be achieved
with commonly
used antiarrhythmic drugs. Even if cardioversion was successful sinus rhythm
can only be maintained in a minority of the patients because of limited
efficacy and safety of the pharmacological compounds. Also, prevention of
thromboembolic events still requires potentially harmful anticoagulation
therapy. Besides the development of means to prevent structural remodeling of
the atria there is great need for new pharmaceutical agents which more
effectively and safely can prolong atrial refractoriness and restore atrial
contraction in order to improve quality of life of AF patients and to reduce
the costs caused by acute therapy, secondary prevention and chronic treatment
of disabilities due to AF.

The aim of the proposed study is to evaluate atrial-specific K+-channels as new
drug targets for the management of AF. Blockers of atrial specific K+-channels
prolong repolarisation exclusively in the atria without proarrhythmic
side-effects on the ventricle and therefore might be of importance for the
management of AF patients.

Right atrial tissue will be obtained from patients undergoing coronary artery
bypass surgery or mitral valve surgery. As a routine procedure the tip of the
right atrial appendage is excised when the venous cannula for the
extra-corporeal circulation is inserted in the right atrium.

In addition, we will work with an animal model. In our group, we have developed
a model of chronically instrumented goats in which we can maintain AF in a
controlled manner. The advantage of this model is the absence of underlying
cardiovascular diseases that may contribute to the development or maintenance
of AF. Tissue from these goats will be studied after 1 week and 3 months of AF.

not applicable