Abstract | AIM: To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF). METHODS AND RESULTS: In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (AT(min)) and maximal activation time (AT(max)) significantly from 35 +/- 12 to 24 +/- 9 and from 97 +/- 38 to 43 +/- 7 ms, respectively. Rotigaptide did not change AT(min) and AT(max) during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction. CONCLUSION:
Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction.
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Authors | Rob F Wiegerinck, Jacques M T de Bakker, Tobias Opthof, Nicolaas de Jonge, Hans Kirkels, Francien J G Wilms-Schopman, Ruben Coronel |
Journal | Basic research in cardiology
(Basic Res Cardiol)
Vol. 104
Issue 3
Pg. 321-32
(May 2009)
ISSN: 1435-1803 [Electronic] Germany |
PMID | 19139945
(Publication Type: Journal Article)
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Chemical References |
- Oligopeptides
- rotigaptide
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Topics |
- Action Potentials
(drug effects, physiology)
- Adult
- Electrophysiology
- Female
- Gap Junctions
(drug effects, metabolism)
- Heart Conduction System
(drug effects, physiopathology)
- Heart Failure
(physiopathology)
- Heart Ventricles
(drug effects, physiopathology)
- Humans
- Male
- Middle Aged
- Myocytes, Cardiac
(drug effects, physiology)
- Neural Conduction
(drug effects, physiology)
- Oligopeptides
(pharmacology)
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