1. Propranolol, as the racemate and the (+)- and (-)-isomers (400 μg/l.) and practolol (50 mg/l.) were tested for their effects on atrial and ventricular rates and on the duration of overdrive suppression (ODI) in isolated perfused cat hearts with surgically-induced heart block.
2. Racemic propranolol and the (+)- and (-)-isomers prolonged ODI and slowed the rate of the ventricular pacemaker; the (+)- and (-)-isomers also reduced the rate of the atrial pacemaker. Practolol shortened ODI and increased the rate of the atrial and ventricular pacemakers.
3. The (+)- and (-)-isomers were more potent than the racemate; the (-)-isomer was more potent than the (+)-isomer. The results suggest there is a stereospecific mechanism involved in the biological distribution of propranolol.
4. Twenty-four hours after reserpine treatment (5 mg/kg, i.p.) practolol continued to increase the rate of the atrial and ventricular pacemakers but did not shorten ODI.
5. The mechanism by which these agents affect myocardial excitability and automaticity is discussed.