Induction of delayed afterdepolarizations and triggered arrhythmias in isolated Purkinje fibers: comparison of resibufogenin and acetylstrophanthidin.
The purpose of this study was to compare the electrotoxicological effects of resibufogenin (RBG) (n = 14) with acetylstrophanthidin (AS) (n = 14) to induce delayed afterdepolarization (DAD) and triggered activity (TA), and their alteration of the electrophysiological properties in sheep cardiac Purkinje fibers using the extracellular electrograms, signal averaging, and standard microelectrode techniques simultaneously. The results indicated: 1) Lower toxic dose of RBG (0.52 mumol.L-1) and AS (0.25 mumol.L-1) induced intracellular and extracellular DAD (DAD-I and DAD-E) at pacing cycle length of 990 and 690 ms. 2) Higher toxic dose of RBG (2.6 mumol.L-1) and AS (5.0 mumol.L-1) induced DAD and TA, nonsustained or sustained premature action potential and oscillatory potentials; 3) At the beginning period of superfusing the drugs, both RBG and AS caused changes of the electrophysiological characteristics. This study demonstrates that the electro-toxicological characteristics and electrophysiological properties of RBG are similar to that of AS and suggests that RBG belongs to the family of digitalis-like drugs.
Xie
J T
JT
Department of Medicine, University of Chicago, IL 60637.
Cunningham
P
P
Shorofsky
S
S
Moscucci
A
A
Cadman
C
C
January
C T
CT
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D002018:Bufanolides / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000633:toxicity*; D004594:Electrophysiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011690:Purkinje Fibers / Q000502:physiology*; D012756:Sheep; D013327:Strophanthidin / Q000031:analogs & derivatives* / Q000633:toxicity
D002018:Bufanolides; D002316:Cardiotonic Agents; C005734:bufogenin; D013327:Strophanthidin; C004681:acetylstrophanthidin