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.
Fleidervish
Ilya A
IA
Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, Israel. fleider@agri.huji.ac.il
Goldberg
Yuri
Y
Ovsyshcher
I Eli
IE
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001919:Bradycardia / Q000209:etiology; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D004562:Electrocardiography; D007267:Injections; D007275:Injections, Intravenous; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018678:Cholinergic Agents; D015221:Potassium Channels; D000109:Acetylcholine