Document Detail

If Inhibition in the Atrioventricular Node by Ivabradine Causes Rate-Dependent Slowing of Conduction and Reduces Ventricular Rate during Atrial Fibrillation.
MedLine Citation:
PMID:  25111327     Owner:  NLM     Status:  Publisher    
BACKGROUND: If channels are functionally expressed in atrioventricular (AV) nodal tissue. Objective: We addressed whether the prototypical If inhibitor, ivabradine, at clinically safe concentrations can slow AV node conduction to reduce ventricular rate (VR) during atrial fibrillation (AF).
METHODS: Effects of ivabradine (0.1 mg/kg, i.v., bolus) were studied in an anesthetized Yorkshire pig (N=7) model of AF and in isolated guinea pig hearts (N=7).
RESULTS: Ivabradine reduced heart rate (p=0.0001) without affecting mean arterial pressure (MAP) during sinus rhythm. The agent lengthened PR intervals in a rate-dependent manner (p=0.0009) by 14±2.7 (p=0.003) and by 25±3.0 msec (p=0.0004) and increased atrial-His (A-H) intervals in a rate-dependent manner (p=0.020) by 10±1.7 and 17±2.8 msec during pacing at 130 and 180 beats/min, respectively (both p=0.0008). Similar rate-dependent effects were observed in isolated guinea pig hearts. Ivabradine slowed VR during AF from 240±21 to 211±25 beats/min (p=0.041). The ivabradine-induced increase in A-H interval was inversely correlated with VR (r=-0.85, p=0.03, at 130 beats/min; r=-0.95, p=0.003, at 180 beats/min). QT and HV intervals, AF dominant frequency [8.5±0.9 to 8.7±1.1 Hz, not significant (NS)], MAP, and left ventricular dP/dt (1672±222 to 1889±229 mmHg/sec, NS) during AF were unaffected.
CONCLUSIONS: Ivabradine's rate-dependent increase in A-H interval is highly correlated with VR during AF. As dominant frequency was unaltered, AV node conduction slowing during high nodal activation rates appears to be the main mechanism of ivabradine's VR reduction. If inhibition in the AV node may provide a promising target to slow VR during AF without depression in contractility.
Richard L Verrier; Rodolfo Bonatti; Ana F G Silva; Julio A P Batatinha; Bruce D Nearing; Gongxin Liu; Sridharan Rajamani; Dewan Zeng; Luiz Belardinelli
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-8
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  -     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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