Arrhythmogenic effects by local left ventricular stretch: effects of flecainide and streptomycin

Mechanical stretch has been shown to provoke arrhythmia. We wanted to analyze ventricular arrhythmia induced by local left ventricular stretch in order to find out, where arrhythmias originate and whether they can be prevented pharmacologically. Isolated rabbit hearts (Langendorff technique) were submitted to increased left ventricular stretch at the left wall by insertion of an additional intraventricular balloon and adjusting the end-diastolic pressure (EDP) to 25 mmHg for 10 min followed by 20 min recovery at normal EDP of 5-8 mmHg. Activation and repolarization processes were investigated by ventricular 256 electrode epicardial mapping. The hearts were treated during the whole procedure either with vehicle, 0.5 μM flecainide (sodium channel blocker) or 100 μM streptomycin (here used as stretch-activated ion-channel blocker). In addition, we performed a series of experiments, in which we enhanced EDP to 30 mmHg (global stretch instead of local stretch) by inflating the left ventricular pressure balloon (strain, 0.148 ± 0.034). Each series was performed with n = 6. Stretch resulted in local strain of 25% at the left wall together with a local slowing of the activation process at the left wall, in a change in the activation pattern, and in ventricular arrhythmia. Coronary flow was not affected. Ventricular arrhythmias originated from the border between the stretched area and the non-stretched region. Flecainide and streptomycin reduced the prolongation of the activation process at the stretched left wall and mitigated the difference in total activation time between left and front wall but only partially prevented arrhythmia. In the additional global stretch experiments relative coronary flow and the other parameters remained unchanged, in particular TAT. Thus, in contrast to the local stretch series, there was no difference in the change in TAT between left and front wall. Only rare single ventricular extrasystoles (<1/min; originating from LV (front and left wall) i.e. from within the stretched region) were seen during stretch (but not at the beginning) and during recovery. Local left ventricular stretch can elicit ventricular arrhythmias. Local slowing of electrical activation seems involved so that the difference in total activation time of the stretched free left wall and the non-stretched increased.