Effects of class I anti-arrhythmic drugs in infarcted tissue.
An in vitro model was used to examine the electrophysiological effects of anti-arrhythmic drugs in infarcted tissue. After 24 h of coronary artery occlusion in the dog, endocardial preparations were removed from the infarcted zone. Intracellular action potentials recorded from surviving Purkinje fibres on the endocardial surface showed reduced maximum upstroke velocity (Vmax), increased action potential duration and enhanced automaticity. The rate-dependent effect of lidocaine on Vmax and conduction was more prominent in Purkinje fibres that survived myocardial infarction than in normal Purkinje fibres. Tocainide, flecainide, and O-demethyl encainide reduced Vmax in both normal Purkinje fibres and Purkinje fibres surviving infarction. Similar to lidocaine, these drugs showed the greatest reduction of Vmax in Purkinje fibres surviving infarction at the shortest stimulation cycle length tested. In contrast, maximal drug effects on action potential duration were observed when long stimulation cycle lengths were used. Our results indicate that most Class I anti-arrhythmic drugs showed rate-dependent properties in normal Purkinje fibres as well as in Purkinje fibres surviving infarction. The increased sensitivity of the ischemic myocardium to anti-arrhythmic drugs resulting in greater reductions of Vmax and conduction may contribute to a greater potency of anti-arrhythmic drugs in the suppression of arrhythmias associated with ischemia. Conversely, while slowing of conduction can abolish re-entry arrhythmias by producing a bidirectional block, further slowing of conduction by anti-arrhythmic drugs can favour the development of new re-entry pathways and may contribute to their pro-arrhythmic effects.
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology; D009203:Myocardial Infarction / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents