Comparative electrophysiological effects of disopyramide and bepridil on rabbit atrial, papillary, and Purkinje tissue: modification by reduced extracellular potassium.
The electrophysiological actions of bepridil were compared with those of disopyramide in rabbit atrial, Purkinje, and papillary muscles in both normokalaemic (5.6 mM K+) and low K+ medium. In normokalaemic medium, the major electrophysiological effects of bepridil (10-40 microM) were a reduction in the maximum rate of rise of phase 0 of the action potential (MRD) of atrial and Purkinje fibres and prolongation of the atrial action potential duration (APD). Higher concentrations (40-100 microM) reduced MRD of papillary muscle without markedly affecting APD. Disopyramide (40-100 microM) reduced MRD and prolonged APD in similar concentrations in all three tissues. Reducing extracellular (EC) K+ to 2.8 mM decreased the effects of bepridil on MRD in all tissues but only significantly reduced the response to disopyramide in papillary muscle. Enhancement of APD prolongation by disopyramide in all tissues resulted when EC K+ was reduced, whereas only papillary muscle APD showed a marked prolongation in response to bepridil. These results demonstrate that the class I effect of bepridil is highly K+ dependent. It may be expected that QTc prolongation produced by both these drugs will be more marked in patients with low serum potassium levels.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015764:Bepridil; D004206:Disopyramide / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D011690:Purkinje Fibers / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits
D011759:Pyrrolidines; D015764:Bepridil; D004206:Disopyramide; D011188:Potassium