Hoffmeister H M, Hepp A, Seipel L
Z Kardiol. 1986 Mar;75(3):176-81.
We investigated the influence of the new class-I antiarrhythmic drug flecainide on myocardial performance and hemodynamic parameters in Wistar rats (2 mg, 4 mg, 8 mg flecainide/kg). Left ventricular and aortic pressures, dp/dt max, cardiac output and additionally isovolumic left ventricular maxima curves were registered 5 min and 15 min after flecainide (n = 28) or saline (controls; n = 12) i.v. infusion (7 min). 2 mg and 4 mg flecainide/kg had no significant effect on isovolumic indices. 5 min after infusion of 8 mg flecainide/kg peak isovolumic left ventricular pressure was reduced by 84.9 +/- 2.6% vs. 95.6 +/- 1.1% (NaCl), mean +/- SEM (p less than 0.01) and peak isovolumic dp/dt max by 44.5 +/- 4.5% vs. 91.5 +/- 3.6% (NaCl), mean +/- SEM (p less than 0.01). Flecainide caused a significant reduction of heart rate (81.9 +/- 4.7%, 2 mg flecainide/kg vs. 95.4 + 2.5% (NaCl), an AV-block occurred only after administration of 8 mg/kg. Mean aortic pressure was decreased after 4 mg and 8 mg flecainide/kg. 8 mg flecainide/kg significantly reduced the cardiac output (73.1 +/- 7.7%, p less than 0.05). 15 min after 2 mg and 4 mg flecainide/kg infusion the determined parameters were normalized, only a dose of 8 mg/kg caused a prolonged hemodynamic depression. Our results demonstrate that in clinically used dosages no hemodynamic side-effects are detectable. A significant reduction of isovolumic indices of myocardial performance occurs only after infusion of 8 mg flecainide/kg. A transfer of laboratory experiments to the clinical situation is only possible with limitations, but our data might indicate that the myocardial and hemodynamic side-effects of flecainide are relatively small at therapeutic dosages.