Differential electrophysiologic effects of mexiletine on normal and hypoxic canine Purkinje fibers.
We studied the effects of increasing concentrations of mexiletine on the active membrane characteristics of canine Purkinje fibers under normal and hypoxic conditions. Under normal conditions, there was a progressive shortening of action potential duration and a small decrease in maximum diastolic potential and overshoot potential. Effective refractory period was shortened by low concentrations but lengthened by higher concentrations. Only at the higher concentrations was Vmax decreased. When the tissue was rendered hypoxic, the shortening effect on action potential duration was attenuated. Low concentrations of mexiletine had a more pronounced effect on maximum diastolic potential and overshoot potential. The reversal of the effect on refractory period occurred at lower concentrations. The effect on Vmax was exaggerated. Hypoxia sensitizes Purkinje fibers to some of the electrophysiologic effects of mexiletine, but other effects are, in fact, attenuated in the presence of hypoxia.
G H
GH
Burke
N D
ND
Berman
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D009467:Neuromuscular Depolarizing Agents; D011437:Propylamines; D008801:Mexiletine; D010100:Oxygen