Biphasic nature of propranolol's microelectrophysiologic effects

The microelectrophysiologic effects of d,l-propranolol were observed to be biphasic when a wide range of concentrations was used in canine atrial tissue; therefore, the 2 isomers were used separately to test the hypothesis that the opposite effects of propranolol could be separated by isomeric isolation. Whole atria were detached from dog hearts and 3 by 0.5 cm strips were cut from the atria. Transmembrane action potentials were monitored from the atrial strips mounted in an isolation chamber containing Tyrode's solution. Concentrations of d-propranolol, l-propranolol, and the d,l-racemate ranging from 0.03 to 1.0 micrograms/ml were added to the bath and the effects observed for 60 minutes. In lower concentrations d,l-propranolol decreased the effective refractory period and activation time while increasing maximal rise velocity, action potential amplitude, and resting membrane potential. Higher concentrations produced the opposite effects. The l-isomer produced effects very similar to those of the lower concentrations of the racemate, whereas the d-form mimicked those effects of the higher concentrations of the racemic mixture. We conclude that d,l-propranolol is capable of exerting 2 opposite electropharmacologic actions, which may be demonstrated by varying the concentration of d,l-propranolol or by separating the isomers.