Rate and time dependent effects of D-sotalol on the monophasic action potential after sudden increase of the heart rate

Experimental and clinical data suggests that almost all Class III antiarrhy thmic agents diminish their ability to prolong cardiac repolarization at fa st heart rates. However, only limited data exists about the time course of efficacy decay of Class iii agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d-sotalol in higher stimulation frequencies following an ab rupt increase in heart rate. This might imitate the situation seen in the d evelopment of paroxysmal tachycardias. Monophasic action potentials were re corded from the right ventricular apex during sinus rhythm and constant sti mulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action poten tial duration at different steady-state heart rates (sinus rhythm: 21.1% +/ - 3.6%; PCL 550 ms: 16.6% +/- 4.3%, 400 ms: 11.2% +/- 2.7%, 330 ms: 5.8% +/ - 2.1%). The prolongation is significantly shorter in higher steady-state p acing, confirming a pronounced reverse-use dependent decrease of the effica cy of d-sotalol at faster stimulation frequencies. After the abrupt increas e in heart rate, the beat-to-beat adaptation of the postdrug action potenti al prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 con secutive beats at the stimulation frequency of the PCL of 400 msec (from 16 .6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and f or the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abru pt increase in heart rate might contribute, to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias.