The effects of dimethyl quaternary propranolol on the electrophysiologic properties of canine cardiac Purkinje fibers.
The effects of dimethyl quaternary propranolol (UM-272) on electrophysiologic properties of canine cardiac Purkinje fibers (PF) were studied using standard microelectrode techniques. In PF superfused with Tyrode's solution, the effects of UM-272, 10- minus 7 to 10- minus 5 M, were studied. In other experiments, UM-272, 3 mg/kg, was injected into donor animals whose blood was used to superfuse isolated PF. Antiarrhythmic concentrations of UM-272 decreased action potential (AP) amplitude, phase 0 upstroke velocity, membrane responsiveness, AP duration and the effective refractory period (the decrease in the effective refractory period was less than that in AP duration). Automaticity of spontaneously firing PF was suppressed. As perfusate potassium concentration was increased, the magnitude of UM-272 effect was accentuated. When the actions of equimolar concentrations of UM-272 and propranolol on PF AP were compared, propranolol attained a steady-state effect more rapidly and tended to depress the AP more markedly. UM-272 did not block epinephrine-induced increases in PF automaticity or the adenylate cyclase activation of PG homogenates induced by epinephrine. These studies indicate that UM-272 has direct effects on the PF AP similar to those of propranolol, but lacks the beta blocking properties of the latter.
D000200:Action Potentials / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010477:Perfusion; D011188:Potassium / Q000502:physiology; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D002395:Catecholamines; D000644:Quaternary Ammonium Compounds; C002616:pranolium; D011433:Propranolol; D000262:Adenylyl Cyclases; D011188:Potassium; D004837:Epinephrine