PMID- 24115934
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20131011
LR  - 20220129
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 4
DP  - 2013
TI  - Electrophysiological and structural determinants of electrotonic modulation of 
      repolarization by the activation sequence.
PG  - 281
LID - 10.3389/fphys.2013.00281 [doi]
LID - 281
AB  - Spatial dispersion of repolarization is known to play an important role in 
      arrhythmogenesis. Electrotonic modulation of repolarization by the activation 
      sequence has been observed in some species and tissue preparations, but to 
      varying extents. Our study sought to determine the mechanisms underlying species- 
      and tissue-dependent electrotonic modulation of repolarization in ventricles. 
      Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular 
      wedges were used to assess epicardial spatial activation and repolarization 
      characteristics. Experiments were supported by computer simulations using 
      realistic geometries. Tight coupling between activation times (AT) and action 
      potential duration (APD) were observed in rat experiments but not in pig. Linear 
      correlation analysis found slopes of -1.03 +/- 0.59 and -0.26 +/- 0.13 for rat and 
      pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 +/- 3.1 
      ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 +/- 
      2.7, p < 0.0001). However, in pig no such difference was observed between the 
      dispersion of APD and RT (17.8 +/- 6.1 vs. 17.7 +/- 6.5, respectively). Localized 
      elevations of APD (12.9 +/- 8.3%) were identified at ventricular insertion sites of 
      rat hearts both in experiments and simulations. Tissue geometry and action 
      potential (AP) morphology contributed significantly to determining influence of 
      electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the 
      slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% 
      when implementing a pig AP in a rat geometry. A modified pig AP, shortened to 
      match the rat APD, showed little coupling between AT and APD with greatly reduced 
      slope compared to the rat AP. Electrotonic modulation of repolarization by the 
      activation sequence is especially pronounced in small hearts with murine-like 
      APs. Tissue architecture and AP morphology play an important role in electrotonic 
      modulation of repolarization.
FAU - Walton, Richard D
AU  - Walton RD
AD  - Faculty of Biological Sciences, Multidisciplinary Cardiovascular Research Centre, 
      School of Biomedical Sciences, Institute of Membrane and Systems Biology, 
      University of Leeds Leeds, UK ; Unite Inserm 1045, Centre de Recherche 
      Cardio-Thoracique, Universite Bordeaux Segalen Bordeaux, France ; L'Institut de 
      Rythmologie et Modelisation Cardiaque, Universite de Bordeaux Bordeaux, France.
FAU - Benson, Alan P
AU  - Benson AP
FAU - Hardy, Matthew E L
AU  - Hardy ME
FAU - White, Ed
AU  - White E
FAU - Bernus, Olivier
AU  - Bernus O
LA  - eng
GR  - G0701776/MRC_/Medical Research Council/United Kingdom
GR  - G0900524/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20131008
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC3792354
OTO - NOTNLM
OT  - action potential duration
OT  - cardiac electrophysiology
OT  - electrotonic current
OT  - heterogeneity
OT  - ventricular repolarization
EDAT- 2013/10/12 06:00
MHDA- 2013/10/12 06:01
PMCR- 2013/10/08
CRDT- 2013/10/12 06:00
PHST- 2013/06/21 00:00 [received]
PHST- 2013/09/18 00:00 [accepted]
PHST- 2013/10/12 06:00 [entrez]
PHST- 2013/10/12 06:00 [pubmed]
PHST- 2013/10/12 06:01 [medline]
PHST- 2013/10/08 00:00 [pmc-release]
AID - 10.3389/fphys.2013.00281 [doi]
PST - epublish
SO  - Front Physiol. 2013 Oct 8;4:281. doi: 10.3389/fphys.2013.00281. eCollection 2013.