Cardiac electrophysiologic properties of dl-propranolol, d-propranolol, l-propranolol and dl-pindolol in anesthetized dogs
Jaillon, P.; Hecklé, J.; Weissenburger, J.; Cheymol, G.
Journal of Pharmacology and Experimental Therapeutics 212(2): 347-353
1980
ISSN/ISBN: 0022-3565 PMID: 6101348 Document Number: 156207
To individually characterize direct and .beta. blocking properties, the cardiac electrophysiologic effects of dl-propranolol (dl-PP) were compared to those of its d-isomer to its l-isomer and to dl-pindolol with His bundle recordings and programmable electrical stimulation in anesthetized dogs. Each group of dogs was randomized to 1 drug on the 1st study day and the other 3 days later. Drugs were injected in 5 cumulative doses at 30 min intervals. A control group received 5 successive saline injections at the same time intervals. Heart rate (HR), atrio-nodal (SH) and His-Purkinje (HV) conduction times and effective and functional refractory periods at a constant driven rate were measured before (basal) and 10 min after each dose of either drug or saline. Comparison of the effects of propranolol isomers showed that they decreased HR and increased SH and atrioventricular [AV] nodal functional refractory periods, l-isomer propranolol with the same potency as and d-isomer propranolol with less potency than dl-PP. dl-PP or its individual isomers did not produce a constant increase of HV, atrial and ventricular effective refractory periods significantly different from the saline control group. dl-Pindolol, with partial .beta.-agonist activity, produced a less important decrease of HR than dl-PP and did not change SH, HV, atrial effective refractory periods and nodal functional refractory periods. Consequences of b blockade are predominant on HR, SH and AV nodal functional refractory periods. Nonspecific membrane stabilization effect exerts no significant action on HV, atrial effective refractory periods and ventricular effective refractory periods. Presence of partial .beta.-agonist activity partially counteracts the electrophysiologic consequences of myocardial .beta. blockade.