Frequency dependent effects of tocainide, quinidine, and flecainide on conduction as reflected in the rise time of the monophasic action potential in the isolated guinea pig heart

Study objective The aim was to evaluate a possible correlation between intraventricular conduction and the rise time of the ventricular monophasic action potential upstroke. Design This evaluation was performed by estimating the onset rate kinetics for changes in the monophasic action potential rise time and cardiac conduction upon abrupt shortening of the interstimulus interval in the in vitro perfused guinea pig heart. Experimental material 21 Duncin Hartley guinea pigs, 520-800 g, were used for the studies. The animals were anaesthetised and the hearts rapidly excised and perfused horizontally in the Langendorff manner. Measurements and main results It was shown that the rise time onset rate (expressed as the inverted number of action potentials needed to reach 63% of the new steady state level) was very fast (greater than 0.5) for tocainide, very slow for flecainide [0.09(SEM 0.009]) and intermediate for quinidine [0.29(0.070)]. These values are similar to onset rates previously reported from studies of Vmax in intracellular recordings. Moreover, similar onset rates were obtained for simultaneously measured frequency dependent changes in cardiac conduction. Conclusions These findings suggest that, at least for drugs restricting sodium entry into the cell, effects on Vmax could be predicted from monophasic action potential rise time data from the isolated guinea pig heart. The possibility of using the monophasic action potential rise time as a measure of local cardiac conduction provides an opportunity for in vivo studies of the temporal beat by beat relationship between conduction and repolarisation, factors that are important for the initiation and maintenance of many arrhythmias.