Author + information
- 1Institute of Cardiovascular Research, the Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Southwest Medical University, Luzhou, Sichuan, China
- 2Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
Previous data have showed that application of ivabradine, a selective blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, leaded to divergent trends regarding proarrhythmic and antiarrhythmic effects in atrial fibrillation (AF). The aim of this study was to investigate the acute effect of ivabradine on atrial electrical remodeling and inducibility of AF in canines with rapid pacing.
In 27 anesthetized open-chest dogs, multi-polar electrode catheters were implanted into the right atrium via external jugular or femoral vein. Dogs were randomly divided into control group, rapid pacing group and ivabradine group. Control group were only recorded without rapid pacing; pacing group were connected with electrical stimulator with sustaining atrial pacing (600 beats/min) for 6 h; ivabradine group were injected by ivabradine (0.5mg/kg/h) through vein passage continuously and were simultaneously paced for 6 h.
After 6 h rapid atrial pacing, application of ivabradine induced a % decrease in sinus rate and prolonged the atrial effective refractory period (AERP) at all sites of atria. Compared with the pacing group, the ivabradine group had fewer incidences of AF and a shorter duration of AF after rapid atrial pacing (P<0.05). In addition, the mRNA expression levels of HCN isoforms were significantly increased in pacing group (P<0.05), but the increasing trend was inhibited in ivabradine group compared with pacing group (P<0.05). The protein expression of HCN channel subunits showed a consistent alteration. Similarly, whole cell patch clamp results showed augmentation of If density in pacing atrial myocytes was significantly attenuated by application of ivabradine (P<0.05).
Ivabradine could effectively reverse the acute electrical remodeling in atria and decrease AF inducibility in dogs with rapid atrial pacing.