Activation and repolarization patterns are governed by different structural characteristics of ventricular myocardium: experimental study with voltage-sensitive dyes and numerical simulations.
BACKGROUND
Substantial progress has been made in our understanding of transmural activation across ventricular muscle through studies of excitation patterns and potential distributions. In contrast, repolarization sequences are poorly understood because of experimental difficulties in mapping action potential durations (APDs) using extracellular electrodes.


RESULTS
Langendorff-perfused guinea pig hearts and isolated coronary-perfused left ventricular sheet preparations were stained with the voltage-sensitive dye RH-421 and optical APs were recorded with a photodiode array. Epicardial maps were constructed using a triangulation method applied to matrices of activation and repolarization times determined from (dF/dt)max and (d2F/dt2)max' respectively. Numerical simulations were carried out based on: (1) a modified Luo-Rudy model; (2) the three-dimensional architecture of ventricular fibers; and (3) the intrinsic spatial distribution of APDs. In ventricular sheets, epicardial stimulation elicited elliptical activation patterns with the major axis aligned with the longitudinal axis of epicardial fibers. When the pacing electrode was progressively inserted from epicardium to endocardium, the major axes rotated gradually, clockwise by 45 degrees, and the eccentricity decreased from 2 to 1.14. Repolarization showed a relatively uniform pattern, independent of pacing site, beginning at the apex and spreading to the base.


CONCLUSIONS
In experiments and simulations, the helical rotation of epicardial excitation isochrones caused by pacing at increasing depth in the myocardium correlated with the helical three-dimensional architecture of ventricular fibers. In contrast, repolarization was independent of the activation sequence and was mainly guided by spatial differences in APDs between apex and base.
Efimov
I R
IR
Department of Cell Biology and Physiology, University of Pittsburgh, Pennsylvania, USA.
Ermentrout
B
B
Huang
D T
DT
Salama
G
G
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D004558:Electric Stimulation; D005260:Female; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000502:physiology*; D010477:Perfusion; D011726:Pyridinium Compounds; D013343:Styrenes; D016276:Ventricular Function
D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D013343:Styrenes; C070534:RH 421