The cardiac electrophysiology of flecainide a new antiarrhythmic agent, was studied in open-chested dogs. At plasma concentrations of 0.4 to 0.7 microgram/ml, flecainide significantly prolonged atrioventricular (AV) conduction. At plasma concentrations greater than 6.5 micrograms/ml, flecainide caused delay throughout the conduction system (77--240%). Low plasma levels of flecainide caused slight prolongation in atrial effective refractory period and AV nodal functional and relative refractory periods. At flecainide levels of 0.7 microgram/ml, ventricular response during atrial fibrillation was significantly slowed. The effects of flecainide on AV nodal and infranodal conduction and refractoriness were significantly enhanced by d,1-propranolol (0.5 mg/kg) but were unaffected by ouabain (0.01 mg/kg). The ventricular fibrillation threshold of supraventricular beats and ventricular premature beats increased with increasing plasma flecainide concentration (122% at 9.3 micrograms/ml and 172% at 1.3 micrograms/ml, respectively). Flecainide slowed ectopic atrial and ventricular pacemakers without affecting sinusor junctional pacemakers.

Animals↗

PubMedDate not supplied

Effects of timolol on action potential characteristics and automaticity in barium-depolarized canine cardiac Purkinje fibers.

To evaluate timolol's ability to antagonize the "slow response" in cardiac tissues, isolated canine cardiac Purkinje fibers were exposed to 0.25 mM barium chloride to induce membrane depolarization, spontaneous automaticity, and slow response action potentials. The effects of timolol on action potential parameters and the cycle length of spontaneous automaticity were tested at concentrations of 10, 100, and 500 micrograms/ml. Timolol significantly depressed the action potential and slowed automaticity only at 100 and 500 micrograms/ml but not at 10 micrograms/ml. Since verapamil and nifedipine have been reported to completely suppress activity in this model at concentrations of 0.2-2.0 micrograms/ml, we conclude that timolol has little direct slow response blocking potency.

Action Potentials↗

PubMedDate not supplied

The effects of the d- and l-optical isomers of propranolol on the ventricular fibrillation threshold.

The minimum current required to induce ventricular fibrillation was determined in 22 sodium pentobarbital anesthetized open chest dogs in the presence of the d- or l-isomers of propranolol at concentrations of 0.2, 0.5, and 1.0 mg/kg. The hearts were paced from the right atrium at a constant basic cycle length of 350 msec and the current was delivered during the vulnerable period to the right ventricle as a 120 msec train of 4 msec square wave pulses at 100 Hz. The l-isomer of propranolol increased the ventricular fibrillation threshold (VFT) above control values at all concentrations; the maximum increase ranged from 17.8 to greater than 420.8% change from control. In contrast, the d-isomer caused only a small increase in the ventricular fibrillation threshold with the maximum increase ranging between 14.0 and 65.2% change from control. The maximum increase in VFT for the racemic mixture of propranolol was 44.7 to greater than 500.0% above control and was similar to the l-isomer alone. Since the beta-blocking potency of the l-isomer is 100 times the potency of the d-isomer we conclude that propranolol's action in increasing the ventricular fibrillation threshold is dependent on its beta-blocking effect.

Animals↗