Binding of diltiazem and verapamil to isolated rat heart mitochondria.

The occurrence of arrhythmias was studied in the "calcium-paradox" model in the isolated rat heart. Clear relationships were found between the duration of calcium-free perfusion and (a) the occurrence of calcium-free-induced electrophysiological changes, (b) the incidence and duration of subsequently induced calcium-repletion arrhythmias and (c) mechanical recovery at the end of the repletion period. The first signs of electrophysiological changes (i.e. decreased heart rate, T-wave amplitude and increased PQ-interval) and irreversible loss of myocardial recovery occurred during or after 60-90 s of calcium-free perfusion. The occurrence of calcium-repletion induced ventricular tachycardia paralleled this onset of irreversible cardiac injury. These results suggest that the process of calcium washout and subsequent sudden calcium overloading may play a role as a trigger in the pathogenesis of ventricular arrhythmias.