Arrhythmogenic effects of digoxin were studied in guinea pig ventricular myocardium driven at a low frequency, using microelectrode technique. Prolonged exposure to digoxin made two distinct phases of arrhythmias to appear: the first phase early occurred without apparent alteration in membrane diastolic potential of the impaled ventricular cells, the second phase was later initiated from oscillatory afterpotentials in diastolic potential. It is proposed that phase 1 of arrhythmias is initiated from oscillatory afterpotentials generated in Purkinje fibers more sensitive to digoxin-induced arrhythmogenic effects than myocardial cells. Phase 2 of arrhythmias would be originated in ventricular muscle fibers. Caffeine abolished oscillatory afterpotentials and suppressed sustained rhythmical activities of phases 1 and 2. The results indirectly confirm the important role of calcium movements between the myoplasm and sarcoplasmic reticulum in the origin of digoxin-induced arrhythmias triggered by oscillatory afterpotentials.

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