title: Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs.
abstract: Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n = 8, ivabradine group) or saline (n = 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac care.
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan. kuemura@ncvc.go.jp.
authors.forename: Kazunori
authors.identifier: http://orcid.org/0000-0003-2900-4702
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Can
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Meihua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukumitsu
authors.affiliation: Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, 565-8565, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced*; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004285:Dogs; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D005260:Female; D006325:Heart Atria / Q000503:physiopathology*; D006339:Heart Rate; D000077550:Ivabradine; D008297:Male; D014630:Vagus Nerve / Q000503:physiopathology*
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: Acute cardiac care; Atrial fibrillation; Effective refractory period; Ivabradine; Vagal nerve