BACKGROUND: Dynamic modulation of repolarization is important in arrhythmogenesis. An inverse relation exists in myocardium between activation time (AT) and action potential duration (APD). We hypothesized that resulting gradients of APD and diastolic interval (DI) interact with restitution properties and modulate the timing of repolarization. METHODS AND RESULTS: Activation-recovery intervals (ARI) were acquired from reconstructed noncontact unipolar electrograms from the left ventricular endocardium in 9 patients (7 male) with normal ventricles. At a basic paced cycle length (median, 450 ms), ARIs shortened along the path of activation, with a mandatory reciprocal increase of DIs. In the median patient, this range of DIs started at 230 ms at the site of earliest activation and increased to 279 ms at the site of latest activation at a basic cycle length of 450 ms. Four consecutive standard S1 to S2 restitution curves were performed. At sites with a longer ARI (and therefore shorter DI) close to the site of stimulation, premature stimulation produced more shortening of ARIs; therefore, the time course of restitution was steeper than at more distal sites. At normal heart rate, the decrease in ARIs along the conduction pathway compensated for later activation. Thus, dispersion in repolarization time (RT) is smaller than dispersion in ARI in a heart with a steep negative AT-ARI relationship. This protective effect is lost in hearts without such a relationship. In the patients with a steep AT-ARI relationship at basic cycle length, this relation is lost after premature stimulation and is a function of prematurity. Thus, dispersion in RT is larger after shortly coupled extra stimuli in patients with a steep AT-ARI relationship. CONCLUSIONS: A complex interplay exists between activation-repolarization coupling and restitution properties, largely driven by ARI and DI gradients. This plays a significant role in the dynamics of repolarization in humans.
BACKGROUND: Dynamic modulation of repolarization is important in arrhythmogenesis. An inverse relation exists in myocardium between activation time (AT) and action potential duration (APD). We hypothesized that resulting gradients of APD and diastolic interval (DI) interact with restitution properties and modulate the timing of repolarization. METHODS AND RESULTS: Activation-recovery intervals (ARI) were acquired from reconstructed noncontact unipolar electrograms from the left ventricular endocardium in 9 patients (7 male) with normal ventricles. At a basic paced cycle length (median, 450 ms), ARIs shortened along the path of activation, with a mandatory reciprocal increase of DIs. In the median patient, this range of DIs started at 230 ms at the site of earliest activation and increased to 279 ms at the site of latest activation at a basic cycle length of 450 ms. Four consecutive standard S1 to S2 restitution curves were performed. At sites with a longer ARI (and therefore shorter DI) close to the site of stimulation, premature stimulation produced more shortening of ARIs; therefore, the time course of restitution was steeper than at more distal sites. At normal heart rate, the decrease in ARIs along the conduction pathway compensated for later activation. Thus, dispersion in repolarization time (RT) is smaller than dispersion in ARI in a heart with a steep negative AT-ARI relationship. This protective effect is lost in hearts without such a relationship. In the patients with a steep AT-ARI relationship at basic cycle length, this relation is lost after premature stimulation and is a function of prematurity. Thus, dispersion in RT is larger after shortly coupled extra stimuli in patients with a steep AT-ARI relationship. CONCLUSIONS: A complex interplay exists between activation-repolarization coupling and restitution properties, largely driven by ARI and DI gradients. This plays a significant role in the dynamics of repolarization in humans.
Authors: Rachel C Myles; Olivier Bernus; Francis L Burton; Stuart M Cobbe; Godfrey L Smith Journal: Am J Physiol Heart Circ Physiol Date: 2010-10-01 Impact factor: 4.733
Authors: Ben Hanson; Jaswinder Gill; David Western; Michael P Gilbey; Julian Bostock; Mark R Boyett; Henggui Zhang; Ruben Coronel; Peter Taggart Journal: Front Physiol Date: 2012-09-24 Impact factor: 4.566
Authors: Tobias Opthof; Peter Sutton; Ruben Coronel; Susan Wright; Panny Kallis; Peter Taggart Journal: Front Physiol Date: 2012-07-03 Impact factor: 4.566
Authors: Claire A Martin; Laila Guzadhur; Andrew A Grace; Ming Lei; Christopher L-H Huang Journal: Am J Physiol Heart Circ Physiol Date: 2011-03-04 Impact factor: 4.733
Authors: Nicholas Child; Ben Hanson; Martin Bishop; Christopher A Rinaldi; Julian Bostock; David Western; Michael Cooklin; Mark O'Neil; Matthew Wright; Reza Razavi; Jaswinder Gill; Peter Taggart Journal: Circ Arrhythm Electrophysiol Date: 2014-05-15