Narrow complex tachycardia with alternating R-R intervals during physical stress: Double ventricular excitation

A 44 year old man presented with recurrent symptomatic palpitations, always appearing during physical stress each with a similiar extent and never during resting periods. He also had fatigue and moderate dyspnoea during the episodes. The past medical history of the patient did not reveal any significant diseases. Findings of the attending physician including 12 lead ECG and echocardiography did not show any abnormality. As there was no electrocardiographic documentation of the episode, a 12-lead Holter evaluation was done

Bertosamil blocks HERG potassium channels in their open and inactivated states

1. Bertosamil is chemically related to the class-III anti-arrhythmic drug tedisamil and has been developed as a bradycardic, anti-ischemic and anti-arrhythmic drug. Its anti-arrhythmic properties might in part be attributed to its block of voltage-dependent potassium channels Kv(1.2), Kv(1.4). and Kv(1.5). However, HERG-potassium channel block as an important target for class-III drugs has not yet been investigated. 2. We investigated the effect of bertosamil on the HERG potassium channel heterologously expressed in Xenopus oocytes with the two-electrode voltage-clamp technique. 3. Bertosamil (70 μM) inhibited HERG tail currrent after a test pulse to 30 mV by 49.3±8.4% (n=5) and the IC(50) was 62.7 μM. Onset of block was fast, i.e. 90% of inhibition developed within 180±8.22 s (n=5), and block was totally reversible upon washout within 294±38.7 s (n=5). 4. Bertosamil-induced block of HERG potassium channels was state-dependent with block mainly to open- and inactivated channels. Half-maximal activation voltage was slightly shifted towards more negative potentials. 5. Steady-state inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited voltage–but no frequency-dependent effects. 6. In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti-arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias