title: Transmural APD gradient synchronizes repolarization in the human left ventricular wall.
abstract: OBJECTIVE
  The duration and morphology of the T wave predict risk for ventricular fibrillation. A transmural gradient in action potential duration (APD) in the ventricular wall has been suggested to underlie the T wave in humans. We hypothesize that the transmural gradient in APD compensates for the normal endocardium-to-epicardium activation sequence and synchronizes repolarization in the human ventricular wall.
  
  
  RESULTS
  We made left ventricular wedge preparations from 10 human donor hearts and measured transmural activation and repolarization patterns by optical mapping, while simultaneously recording a pseudo-ECG. We also studied the relation between local timings of repolarization with the T wave in silico. During endocardial pacing (1 Hz), APD was longer at the subendocardium than at the subepicardium (360 ± 17 vs. 317 ± 20 ms, P < 0.05). The transmural activation time was 32 ± 4 ms and resulted in final repolarization of the subepicardium at 349 ± 18 ms. The overall transmural dispersion in repolarization time was smaller than that of APD. During epicardial pacing, the dispersion in repolarization time increased, whereas that of APD remained similar. The morphology of the T wave did not differ between endocardial and epicardial stimulation. Simulations explained the constant T wave morphology without transmural APD gradients.
  
  
  CONCLUSIONS
  The intrinsic transmural difference in APD compensates for the normal cardiac activation sequence, resulting in more homogeneous repolarization of the left ventricular wall. Our data suggest that the transmural repolarization differences do not fully explain the genesis of the T wave.
authors.affiliation: Department of Biomedical Engineering, George Washington University, 5000 Science and Engineering Hall, 800 22ng Street NW, Washington, DC 20052, USA.
authors.forename: Bastiaan J
authors.initials: BJ
authors.lastname: Boukens
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Sulkin
authors.affiliation: Department of Biomedical Engineering, George Washington University, 5000 Science and Engineering Hall, 800 22ng Street NW, Washington, DC 20052, USA.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Gloschat
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Fu Siong
authors.initials: FS
authors.lastname: Ng
authors.affiliation: Institut LIRYC, and Institut de Mathématiques de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Vigmond
authors.affiliation: Department of Biomedical Engineering, George Washington University, 5000 Science and Engineering Hall, 800 22ng Street NW, Washington, DC 20052, USA Department of Biomedical Engineering, Washington University, St. Louis, MO, USA Institut LIRYC, and Institut de Mathématiques de Bordeaux, Université de Bordeaux, Bordeaux, France efimov@gwu.edu.
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D002648:Child; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016277:Ventricular Function, Left
keywords: Human; Optical mapping; Repolarization; T wave