Effects of myocardial hypoxia on digitalis-induced toxicity in the isolated heart of guinea pigs and cats.
The effects of hypoxia on the tolerance of myocardium to the toxic actions of digitalis were studied in isolated heart muscle preparations. Perfusion of Langendorff preparations of guinea-pig heart with a hypoxic solution failed to alter Na, K-ATPase with respect to its activity, its sensitivity to inhibition by dihydrodigoxin, or the number of [3H]ouabain binding sites and their affinity for ouabain, when these activities were estimated in ventricular muscle homogenates obtained after the hypoxic perfusion. Hypoxia potentiated the development of digoxin-induced contracture, as well as digoxin-induced changes in maximal upstroke velocity and the amplitude of action potentials, and the resting transmembrane potential in atrial and ventricular muscle preparations of guinea-pig heart. Under hypoxic conditions, however, digoxin failed to induce arrhythmias. In Purkinje fibers of cat heart, the time to onset of digoxin-induced arrhythmias, or the development of afterdepolarizations, was not affected by hypoxia. These results indicate that hypoxia alters the nature of toxic effects of digitalis in isolated heart muscle preparations, the development of contracture instead of arrhythmias being the primary toxicity in hypoxic muscle.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002415:Cats; D003327:Coronary Disease / Q000150:complications; D004071:Digitalis Glycosides / Q000633:toxicity*; D004077:Digoxin / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism; D010100:Oxygen; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D014316:Tritium
D004071:Digitalis Glycosides; D014316:Tritium; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen