How increased sodium influx enhances digoxin-induced arrhythmias in guinea-pig atrial muscle.
The hypothesis that digitalis-induced arrhythmias occur when Na,K-ATPase inhibition exhausts the sodium pump reserve capacity, producing an accumulation of intracellular Na+, was tested by reducing the reserve capacity in isolated left atrial muscle of guinea pig heart and estimating specific digoxin binding and Na,K-ATPase activity in atrial muscle homogenized at the onset of digoxin-induced arrhythmias. Reductions in reserve capacity were produced by either increasing the stimulation frequency of the atrial muscle or adding a sodium ionophore, monensin, to the media bathing the tissue. As stimulation frequency was increased, both the time required to produce arrhythmias with a given concentration of digoxin and the amount of digoxin bound to sarcolemmal Na,K-ATPase at the onset of arrhythmias were reduced. Similarly, monensin treatment produced reductions in the time to arrhythmia and in digoxin binding and Na,K-ATPase inhibition observed at the onset of arrhythmias. These results support the above proposal suggesting that a decrease in reserve capacity of the sodium pump enhances cardiac sensitivity to digitalis-induced arrhythmias.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D004077:Digoxin / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D004558:Electric Stimulation; D005663:Furans / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D012964:Sodium / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013997:Time Factors
D005663:Furans; D010042:Ouabain; D004077:Digoxin; D012110:Reserpine; D008985:Monensin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase