Flecainide alters the cardiac microscopic activation pattern. An in-vitro study using voltage sensitive dyes

In order to evaluate whether flecainide may alter microscopic activation patterns, isolated guinea pig papillary muscles (paced at a rate of 1 Hz or 3 Hz respectively, superfused with saline Tyrode solution at 37 degrees C) were exposed to 1.5 mumol l-1 flecainide. The muscles were stained with the voltage sensitive dye di-4-ANEPPS and excited with argon ion laser light at 514 nm. Fluorescence (F) was measured through a OG 570 filter by a 16*16 photodiode array (spatial resolution 180 microns). Activation times were determined the minimum -dF/dt. From these data on activation sequence could be determined. From the activation times of a given photodiode and of the surrounding diodes, which were activated later, vectors were calculated giving direction and velocity of the local activation wave. The isochrones under control conditions and under treatment were compared directly in a qualitative manner. For quantification the percentage of vectors with similar direction (deviation < 5 degrees) under control conditions and after treatment were determined. Under the influence of flecainide, the percentage of similar vectors decreased from 34% to 24% (1 Hz) or from 27% to 17% (3 Hz) (n = 6). Analysis of the isochrones showed that the propagation velocities were altered inhomogeneously. The total activation time (TAT) of the papillary muscles (calculated from the delay between the end of the stimulus and the activation of the last photodiode) was increased from 10.2 to 11.5 ms at 3 Hz, but was only slightly prolonged at the lower frequency (from 10.9 to 11.1 ms at 1 Hz). These results demonstrate that (a) flecainide can alter the microscopic activation patterns (b) that this effect has a use-dependent component and (c) the total activation time is slowed by flecainide. These effects may be linked to the proarrhythmic and antiarrhythmic activity of the drug.