Comparative investigations on the antiarrhythmic and electrophysiologic effects of class I-IV antiarrhythmic agents following acute coronary artery occlusion

The effects of class I to IV antiarrhythmic drugs on ventricular arrhythmias, particularly ventricular fibrillation, in relation to epicardial conduction delay during acute myocardial ischaemia were investigated in 40 open-chest anaesthetized dogs. In these animals transient coronary artery occlusion lasting 20 minutes was performed. Sixteen dogs served as controls; four groups of 6 dogs each received lidocaine (2 mg kg−1 + 50 μg kg−1 over 20 minutes), metoprolol (2 mg kg−1 i.v.), d-sotalol (5 mg kg−1 i.v.) and verapamil (0.25 mg kg−1 i.v.), respectively 5 minutes prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group conduction delay displayed a bimodal time course in the ischaemic area with a maximum of 38±10 ms 6 minutes after coronary occlusion followed by a partial improvement after 12 to 15 minutes. After pretreatment with lidocaine the peak conduction delay in the ischaemic area was significantly increased (43.2±12), whereas metropolol (21.5±1.9), d-sotalol (16.6±3.7) and verapamil (16.3±3.1) significantly reduced conduction delay. Correspondingly, ventricular arrhythmias and fibrillation were almost completely prevented by metoprolol, d-sotalol or verapamil, but increased by lidocaine. In accordance with recent reports in the literature our results show that delayed and inhomogeneous activation of the ischaemic myocardium plays an important role in the genesis of ventricular arrhythmias during acute myocardial ischaemia; thus a reduction in conduction delay seems to be a precondition for antiarrhythmic drug action, at least at the onset of ischaemia, while a further increase in conduction delay as provided by class I antiarrhythmic agents such as lidocaine can be supposed to be arrhylhmogenic.