Gender disparities in torsade de pointes ventricular tachycardia.
BACKGROUND
Gender disparities in the incidence of torsade de pointes (TdP) ventricular tachycardia exist, but the mechanisms in humans are unresolved. We addressed this issue using a mathematical model of a human ventricular cell.


METHODS
We implemented gender differences in the Priebe-Beuckelmann model cell by modifying the amplitudes of the L-type Ca(2+) current (I(Ca,L)), transient outward K(+) current (I(to)), and rapid component of the delayed rectifier K(+)current (I(Kr)), according to experimental data from animal male and female hearts. Gender disparities in electrical heterogeneity between transmural layers (subepicardium, midmyocardium, subendocardium) were implemented by modifying various ion currents according to experimental data.


RESULTS
Action potentials in female cells have longer durations and steeper duration versus frequency relationships than male cells. In the female cells, electrical heterogeneity between transmural layers is larger and the susceptibility to early afterdepolarisations is higher than in male cells.


CONCLUSIONS
Gender-related differences in I(Ca,L), I(to), and I(Kr )may explain the gender disparities in human cardiac electrophysiology. Female cells have an increased susceptibility to early afterdepolarisations following mild reductions in net repolarising forces. Combined with their greater electrical heterogeneity, this renders them more vulnerable to TdP. (Neth Heart J 2007;15:405-11.).
Verkerk
A O
AO
Department of Physiology, Heart Failure Research Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Wilders
R
R
Tan
H L
HL