Arrhythmogenic effects of theophylline in human atrial tissue

We studied the effects of theophylline on the transmembrane action potential and the contractile force of human atrial fibers obtained from the hearts of 15 patients, undergoing corrective open-heart surgery. Atrial fibers were perfused with Tyrode solution and driven electrically at a constant rate of 60 beats per min. Theophylline (0.1-1 mM) steepened the diastolic depolarization, increased the amplitude of oscillatory potential during diastole and facilitated the development of spontaneous slow response action potentials. These arrhythmogenic effects of theophylline were suppressed after diltiazem (0.1-0.3 microM) pretreatment. The present findings provide the electrophysiologic evidence that abnormal atrial automaticity as a result of triggered activity may be the underlying cause for atrial ectopic activity and multifocal atrial tachycardia in patients taking theophylline.