THE RISE-TIME OF THE MONOPHASIC ACTION-POTENTIAL - A NEW INDEX OF LOCAL USE-DEPENDENT CONDUCTIVITY BY SODIUM-CHANNEL BLOCKERS IN HUMAN MYOCARDIUM

The kinetics of global use-dependent conduction slowing produced by so dium 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 n ot been investigated. We examined whether the rise time of the monopha sic action potential would be clinically useful as a marker of the loc al use-dependent decrease in conductivity by sodium channel blockers. In 12 patients without organic heart disease, monophasic action potent ials (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 incre ased from 100/min to 150/min. The rise time, defined as the interval f rom the pacing pulse to the first peak deflection of the monophasic ac tion 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 con stants 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, respecti vely. The rate constant of the rise time was closely correlated with t hat of the QRS width. The present results are very closely comparable with the onset rate constants of use-dependent block of the maximum ra te of depolarization in in vitro studies. These results suggest that ( 1) the rise time is a good indicator of local use-dependent decrease i n conductivity by sodium channel blockers in human hearts and (2) the local use-dependent decrease in conductivity has kinetics similar to t hose of use-dependent sodium channel blocks.