Arrhythmogenic effects of mexiletine in infarcted Purkinje tissues.
The electrophysiologic effects of mexiletine on canine subendocardial Purkinje's fibers were examined 24 hours after a two-stage ligation of the left anterior descending coronary artery. Transmembrane potentials were recorded simultaneously in normal (NZ) and infarcted (IZ) zones before and during superfusion with mexiletine. Mexiletine (3, 6, and 9 mg/l) reduced the values of maximum diastolic potential (MDP), action potential amplitude (APA), and maximum rate of phase 0 depolarization (Vmax). The effective refractory period (ERP) was lengthened by the drug. These findings are consistent with the actions of class IB antiarrhythmic drugs. In 42% of the preparations examined, repetitive responses were induced at or near the ERP during superfusion with 3 mg/l mexiletine. These extra responses were no longer elicited during superfusion with 6 mg/l mexiletine. A mechanism for the origin of these reentrant-type arrhythmias based on the action of mexiletine is presented.
Han
J
J
Department of Medicine (Cardiology), Albany Medical College of Union University, NY 12208.
Derhsam
G H
GH
O'Connell
D P
DP
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000503:physiopathology; D011930:Reaction Time / Q000502:physiology
D008801:Mexiletine