The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts
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The optical isomers of the beta blocking agent propranolol exert beta receptor blocking as well as membrane stabilizing effects. The latter is thought to be responsible for the antiarrhythmic effect of the drug.
In this study we quantified the electrophysiological effects of both isomers of propranolol on the conduction and pacemaker system of the heart. The experiments were performed on isolated hearts using a special ECG recording and stimulation technique. To abolish isoproterenol's beta adrenergic stimulatory effect on heart rate, 30-times higher concentrations of (+)propranolol were necessary than of (−)propranolol in order to be consistent. Both isomers caused a similar and marked slowing of conduction velocity through the bundle of His and ventricular myocardium. Also, heart rate, as well as atrio-ventricular conduction velocity were significantly slowed by a concentration of 10 μM of either drug, (−)propranolol being slightly more effective. Only in the presence of (−)propranolol did significant changes of atrio-ventricular and His-bundle conduction occur at a concentration of 1 μM. During programed stimulation sinus node recovery time was more prolonged by (−)propranolol than during perfusion with (+)propranolol. The highest rate of pacing with 1∶1 conduction of the sino-atrial conduction, the atrial and ventricular myocardium was significantly depressed to a comparable degree by either isomers of propranolol. These effects appear to be primarily responsible for the antiarrhythmic effects of both isomers. Because of the minor effects of (+)propranolol on sinus- and AV-node activity, as well as on beta adrenergic receptors, this isomer may have potential clinical importance in the treatment of arrhythmias.
Key wordsbeta receptor propranolol enantiomers refractoriness conduction
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- 1.Barret M, Cullum VA (1968) The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias. Br J Pharmac 34:43–55Google Scholar
- 3.Coltart DJ, Meldrum S (1971) The effect of racemic propranolol and racemic practolol on the human and canine transmembrane action potential. Arch Intern Pharmacodyn 192:188–197Google Scholar
- 6.Lindner W, Leitner Ch, Uray G (1984) Liquid chromatographic separation of enantiomeric alkanolamine via diastereomerie tartaric acid monosters. J Chromatogr 316:605–616Google Scholar
- 8.Myers MG, Lewis PG, Reid JL, Dollery CT (1973) Cardiovascular effects of centrally administered d-, 1- and d1-propranolol in the conscious rabbit. Eur J Clin Invest 3:257–261Google Scholar
- 10.Pruett JK, Walle T, Walle UC (1980) Propranolol effects on membrane repolarization in isolated canine Purkinje fibers: Treshold tissue content and the influence of exposure time. J Pharmacol Exp Therap 215:535–543Google Scholar
- 12.Roman E, Ruiz F, Perez D, Hernandez J (1987) The effects of propranolol stereoisomers on nomotopic and ectopic cardiac automaticity in the heart. Chem Pathol Pharm 58:139–142Google Scholar
- 16.Stark G, Stark U, Tritthart HA (1989) Assessment of the conduction of the cardiac surface and stimulation technique (SST-ECG) in Langendorff perfused mammalian hearts. J Pharmacol Method, in pressGoogle Scholar
- 17.Thompson KA, Roden DM, Wood AJ, Siddoway LA, Barbey JT, Woosley RL (1984) Suppression of ventricular arrhythmias by dextro propranolol in man. Circulation 70:Supp II 1764Google Scholar
- 18.Tritthart HA (1983) Wirkspektrum von Antiarrhythmika und Betarezeptorenblockern. In: Lüderitz B (ed) Herzrhythmusstörungen. Springer-Verlag, Berlin Heidelberg New York, S 141–166Google Scholar
- 19.Tritthart HA (1988) Therapie der Erregungsbildungs- und-leitungsstörungen. In: Roskamm H, Reindell H (eds) Herzkrankheiten. Springer-Verlag, Berlin Heidelberg New York, S 660–675Google Scholar