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

Area of Science:

• Cardiac Electrophysiology
• Pharmacology
• Biophysics

Background:

• Flecainide is a Class Ic antiarrhythmic drug.
• Its effects on microscopic cardiac activation patterns are not fully understood.
• Understanding these effects is crucial for evaluating its proarrhythmic and antiarrhythmic potential.

Purpose of the Study:

• To investigate the impact of flecainide on microscopic activation patterns in isolated guinea pig papillary muscles.
• To determine if flecainide alters the direction and velocity of cardiac activation waves.
• To assess the use-dependency of flecainide's effects on cardiac electrophysiology.

Main Methods:

• Isolated guinea pig papillary muscles were superfused and paced at 1 Hz or 3 Hz.
• Muscles were exposed to flecainide (1.5 µmol L⁻¹).
• Voltage-sensitive dye (di-4-ANEPPS) and a photodiode array were used to map activation patterns and calculate wave propagation vectors.

Main Results:

• Flecainide decreased the percentage of consistent activation wave vectors, indicating altered microscopic patterns.
• This effect was more pronounced at 3 Hz (17% vs. 27%) compared to 1 Hz (24% vs. 34%).
• Total activation time (TAT) increased from 10.2 to 11.5 ms at 3 Hz, with a smaller increase at 1 Hz.

Conclusions:

• Flecainide significantly alters microscopic cardiac activation patterns.
• The observed effects exhibit use-dependency, being more prominent at higher pacing frequencies.
• Flecainide slows total activation time, potentially contributing to its complex clinical electrophysiological effects.