title: Dronedarone attenuates the duration of atrial fibrillation in a dog model of sustained atrial fibrillation.
abstract: Atrial fibrillation (AF) is a supraventricular arrhythmia that leads to a decrease in cardiac output and impairs cardiac function and quality of life. Dronedarone has an atrial-selective property and has been used for management of AF in humans, but limited information is available in dogs. This study was designed to evaluate efficacy of dronedarone in attenuating the duration of AF in dog model of sustained AF. Six beagle dogs were anesthetized with isoflurane and instrumented to measure atrial action potential duration (aAPD) and atrial effective refractory period (AERP). Then AF was induced by rapid right atrial pacing (20 V, 40 Hz) simultaneously with infusion of phenylephrine (2 µg/kg/min, intravenously) for 20 min. The duration of sustained AF was recorded, and the animals were allowed to recover. Dronedarone was given at a dose of 20 mg/kg, BID, orally for 7 days. On the last day, the dogs were anesthetized again to record aAPD and AERP, and AF was induced with the same procedure as described above. The results showed that after dronedarone administration the aAPD was lengthened significantly from 76.4 ± 4.2 ms to 91.2 ± 3.9 ms (P<0.05) and AERP was prolonged significantly from 97.5 ± 2.8 ms to 120 ± 4.8 ms (P<0.05). The duration of sustained AF was also significantly attenuated after receipt of dronedarone (P<0.05). It can be suggested that oral dronedarone attenuates the duration of sustained AF in a dog model of AF by extending the AERP more than the aAPD, causing post-repolarization refractoriness. Hence, dronedarone may be useful for management of AF in dogs.
authors.affiliation: Animal Physiology Program, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri Dunant Road, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Nakkawee
authors.initials: N
authors.lastname: Saengklub
authors.affiliation: Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri Dunant Road, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Vudhiporn
authors.initials: V
authors.lastname: Limprasutr
authors.affiliation: Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri Dunant Road, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Suwanakiet
authors.initials: S
authors.lastname: Sawangkoon
authors.affiliation: QTest Labs, Ltd., 6456 Fiesta Drive, Columbus, Ohio 43235, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hamlin
authors.affiliation: Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri Dunant Road, Pathumwan, Bangkok 10330, Thailand.|Research clusters: research study and testing of drug's effect related to cardiovascular system in laboratory animal, Chulalongkorn University, 39 Henri Dunant Road, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Anusak
authors.initials: A
authors.lastname: Kijtawornrat
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D000077764:Dronedarone; D006325:Heart Atria / Q000503:physiopathology; D006801:Humans; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors
chemical_list: D000077764:Dronedarone; D000638:Amiodarone
keywords: atrial fibrillation; dog; dronedarone; post-repolarization refractoriness