The kinetics of global use-dependent conduction slowing produced by sodium channel blockers in the human heart, estimated as a change in the QRS width, are known to be similar to those of use-dependent block of the maximum rate of depolarization in in vitro studies. However, the kinetics of the regional use-dependent decrease in conductivity have not been investigated. We examined whether the rise time of the monophasic action potential would be clinically useful as a marker of the local use-dependent decrease in conductivity by sodium channel blockers. In 12 patients without organic heart disease, monophasic action potentials (MAPs) were recorded at the right ventricular endocardium using a contact electrode before and after the administration of disopyramide (n = 6, 2 mg/kg, iv) or pilsicainide (class Ic agents, n=4, 1 mg/kg, iv, and n=2, 150 mg, po) while the stimulus frequency was abruptly increased from 100/min to 150/min. The rise time, defined as the interval from the pacing pulse to the first peak deflection of the monophasic action potential, and the QRS width were measured simultaneously. In the absence of the sodium channel blockers, the abrupt increase in heart rate did not alter the QRS width or the rise time. In the presence of the agents, both variables were lengthened exponentially. The rate constants of onset changes in the QRS width and the rise time were 2.1 + 0.5 beats and 2.1 + 0.4 beats after the administration of disopyramide, and 7.5 + 3.0 beats and 8.2 + 4.0 beats after pilsicainide, respectively. The rate constant of the rise time was closely correlated with that of the QRS width. The present results are very closely comparable with the onset rate constants of use-dependent block of the maximum rate of depolarization in in vitro studies. These results suggest that (1) the rise time is a good indicator of local use-dependent decrease in conductivity by sodium channel blockers in human hearts and (2) the local use-dependent decrease in conductivity has kinetics similar to those of use-dependent sodium channel blocks.
- Monophasic action potential
- Rise time
- Use-dependent block
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine