Bolus injection of acetylcholine terminates atrial fibrillation in rats

It is well established that a tonic increase in the availability of the atrial muscarinic K(+) channels, either by enhanced vagal tone or by steady infusion of a low-dose of cholinergic or adenosine receptor agonists, promotes the genesis of atrial fibrillation. Here, we aimed to test the hypothesis that bolus administration of a muscarinic receptor agonist would destabilize and terminate atrial arrhythmia by uniformly and transiently activating K(+) channels throughout the atria, and that if the agonist was rapidly hydrolysable, it would dissipate before the more tonic, pro-arrhythmic effects could take hold. The episodes of untreated atrial fibrillation, induced in anesthetized rats by programmed electrical stimulation via trans-esophageal bipolar catheter, lasted on average 8.6+/-2.2 min (n=32). Intravenous injection of a model hydrolysable muscarinic agonist, acetylcholine (0.2 mg/kg body weight), converted atrial fibrillation into sinus rhythm within 8.4+/-1.9 s (n=10, P<0.05). The termination of an atrial fibrillation episode was always accompanied by transient bradycardia; the sinus rhythm gradually accelerated and reached pre-atrial fibrillation values within 10-20 s of injection. In conclusion, our evidence indicates that bolus administration of rapidly hydrolysable muscarinic agonist could be an effective way to pharmacologically terminate atrial fibrillation and restore sinus rhythm.