ELECTROPHYSIOLOGICAL EFFECTS OF FLECAINIDE ACETATE ON STRETCHED GUINEA-PIG LEFT ATRIAL MUSCLE-FIBERS

The electrophysiological effects of flecainide acetate (3 x 10(-6) M) on stretched atrial tissue were investigated using guinea-pig left atr ial muscle fibers. Before stretching. the resting membrane potential w as not affected by flecainide at 1 Hz, although the overshoot potentia l (Eov) and the action potential duration at 50% repolarization (APD50 ) were slightly but significantly decreased by 2 +/- 1 mV and 2 +/- 1 msec, respectively. The effective refractory period (ERP) was increase d by 3 +/- 1 msec. The reduction of Vmax was 20.6 +/- 1. 2%. The half- maximum potential (Vh) of the relationship between Vmax and the restin g potential was shifted to become more negative by flecainide (from -6 0.6 +/- 2.1 mV to -63.2 +/- 1.7 mV). After 90-120 min of washout with drug-free Tyrode's solution, the tissue was mechanically stretched to 150% of its slack length. Stretching significantly decreased the Vmax by 16.9 +/- 3.1%, along with a slight but significant increase in ERP (3 +/- 1 msec) and shifted Vh to become more negative (from -60.6 +/- 2.1 to - 63.1 +/- 1.5 mV). In the presence of flecainide, Vmax further decreased by 20.2 +/- 2.6%, and Vh shifted from -63.1 +/- 1.8 to -65. 0 +/- 1.5 mV. Comparison with the control unstretched fibers showed th at flecainide significantly decreased Vmax by 34.0 +/- 2.7%, reduced t he resting membrane potential by 3 +/- 1 mV, decreased Eov by 4 +/- 1 mV, and shifted Vh from -60.6 +/- 2.1 to -65.0 +/- 1. 5 mV, while the APD50 and ERP did not change. In conclusion, the reduction of Vmax in the presence of flecainide was much greater in the stretched atrial mu scle fibers than in the unstretched fibers, because the Vmax-resting p otential relationship was shifted towards more negative potentials by both flecainide and stretching. These results suggest that flecainide exerts a stronger antiarrhythmic action on stretched atrial muscle fib ers than on normal fibers.