Increased cyclic GMP in atrial fibrillation

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF, and in dogs subjected to high frequency (230 or 410/min) atrial pacing. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP), and the effect of atropine (0.1 mg/kg) on AFT were determined. Plasma levels of c-GMP and c-AMP were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. The c-GMP level began to increase significantly 15 min after the initiation of pacing at the higher rate (410/min) but not at the lower rate, compared to the prepacing value. The c-GMP level continued to rise until the end of pacing in the animals paced at 410/min. Although Dbc-GMP induced a dose-dependent decrease in AFT, atropine did not prevent the decrease in AFT by Dbc-GMP. In contrast, c-AMP levels were not significantly affected in any of these experiments. Clinical assessment revealed that patients had almost four times higher c-GMP level during AF than during sinus rhythm, though c-AMP levels in these patients did not change significantly during the attack of AF. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.