The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts.
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 microM 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 microM. During programmed 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.
Stark
G
G
Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
Stark
U
U
Lueger
A
A
Bertuch
H
H
Pilger
E
E
Pietsch
B
B
Tritthart
H A
HA
Lindner
W
W
D000818:Animals; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D013237:Stereoisomerism
D011433:Propranolol; D007545:Isoproterenol