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

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. Returned for 1. Revision: 14 July 2008 1. Revision received: 26 August 2008 Returned for 2. Revision: 19 September 2008 2. Revision received: 31 October 2008 Returned for 3. Revision: 17 November 2008 3. Revision received: 18 November 2008