Effects of beta-blockade on atrial and atrioventricular nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation in pigs

Despite their widespread use in atrial fibrillation, the effects of beta-adrenoceptor blockers on atrial and atrioventricular (AV) nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation have been incompletely characterised. In particular, it is unknown whether additional sodium channel (class I) blocking effects play a role. Effects of bisoprolol (no class I effect) and metoprolol (mild class I effect) were therefore compared in 12 open-chest pigs. Atrial and AV-nodal effective refractory periods were determined at pacing cycle length 500 ms and 300 ms. Atrial fibrillation was then induced by premature stimulation and topical application of metacholine, and atrial fibrillatory intervals and ventricular intervals were recorded. After resumption of sinus rhythm, bisoprolol 0.1 mg/kg or metoprolol 0.3 mg/kg was administered, and measurements were repeated. Also, effects on plasma catecholamines and signal-averaged QRS duration were determined. Both bisoprolol and metoprolol prolonged atrial and AV-nodal effective refractory periods at both pacing cycle lengths, however, no differences were noted between the two drugs. No significant effects were observed on atrial and ventricular intervals during atrial fibrillation. Plasma catecholamines were low and unaffected by either drug, as was the QRS duration. It is concluded that the mild class I effect of metoprolol does not play a role in atrial fibrillation. Also, the results confirm the clinical notion that beta-blockers exert insignificant effects during atrial fibrillation in the setting of low sympathetic tone.