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

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.

• 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)

Chemical References

• Oligopeptides
• rotigaptide

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)