Effect of quinidine on differing sensitivities of Purkinje fibers and myocardium to inhibition of monovalent cation transport by digitalis in dogs.
Studies have implicated quinidine in increasing serum digoxin levels, resulting in serious arrhythmias. Arrhythmias caused by digitalis intoxication are thought to originate in Purkinje fibers. Thus, the extent of inhibition of monovalent cation-active transport in Purkinje fibers and myocardium may explain the enhanced toxicity of the combined administration of digoxin and quinidine. Monovalent cation transport was assessed by measuring the uptake of the potassium analog rubidium in samples of myocardium and Purkinje fibers after in vitro exposure to ouabain and after long-term administration of digoxin and quinidine or digoxin alone. A group of dogs received chronic digoxin administration and achieved a steady-stage digoxin administration and achieved a steady-stage digoxin level of 2.1 +/- 0.3 ng/ml. Quinidine administered intravenously caused a 134% increase in the serum digoxin level. The transport in myocardium was unchanged, while it was reduced to 40% of control levels in Purkinje fibers. The difference in sensitivity between Purkinje fibers and myocardium may explain the finding that digitalis-toxic arrhythmias arise in Purkinje fibers and that quinidine, when combined with digitalis, increases the incidence of such arrhythmias.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology / Q000633:toxicity*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D012413:Rubidium / Q000378:metabolism
D010042:Ouabain; D004077:Digoxin; D011802:Quinidine; D012413:Rubidium