OPC-88117 suppresses early and delayed afterdepolarizations and arrhythmias induced by cesium, 4-aminopyridine and digitalis in canine Purkinje fibers and in the canine heart in situ.
The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.
Graham
B
B
Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis.
Gilmour
R F
RF
Stanton
M S
MS
Zipes
D P
DP
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002317:Cardiovascular Agents; D002586:Cesium; D004070:Digitalis; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006327:Heart Block / Q000517:prevention & control; D006329:Heart Conduction System; D008564:Membrane Potentials / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011690:Purkinje Fibers / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*
D002317:Cardiovascular Agents; D010879:Piperazines; D015363:Quinolones; C061263:8-methyl-3-(4-methyl-1-piperazinyl)-2(1H)-quinolinone; D002586:Cesium; D015761:4-Aminopyridine