on February 18, 2009
Published online before print February 18, 2009, doi: 10.1161/CIRCEP.108.785352
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Original Article |
The Interaction of Activation-Repolarisation Coupling and Restitution Properties in Humans
1 University College London;
2 University College Hospitals;
3 Guy's and St Thomas' Hospital Trust;
4 Brighton and Sussex Medical School
5 E-mail: peter.taggart{at}uclh.org
Background—Dynamic modulation of repolarisation is important in arrhythmogenesis. An inverse relation exists in myocardium between activation time (AT) and action potential duration (APD). We hypothesised that resulting gradients of APD and diastolic interval (DI) interact with restitution properties and modulate the timing of repolarisation.
Methods and Results—Activation-recovery intervals (ARI) were acquired from reconstructed noncontact unipolar electrograms from the left ventricular endocardium in 9 patients (7M) 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-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-repolarisation coupling and restitution properties, largely driven by ARI and diastolic interval gradients. This plays a significant role in the dynamics of repolarisation in humans.
Key Words: arrhythmia • conduction • electrophysiology • repolarisation • restitution
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