The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Wiegerinck
Rob F
RF
Experimental Cardiology Group (ECG), Dept. of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands.
de Bakker
Jacques M T
JM
Opthof
Tobias
T
de Jonge
Nicolaas
N
Kirkels
Hans
H
Wilms-Schopman
Francien J G
FJ
Coronel
Ruben
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000328:Adult; D004594:Electrophysiology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology
D009842:Oligopeptides; C477643:rotigaptide