Enhanced ouabain sensitivity of the heart and myocardial sodium pump in aged rats

Tolerance to arrhythmogenic actions of digitalis decreases with advanced age. To determine if aged myocardium has reduced glycoside tolerance, ouabain sensitivity and associated biochemical changes were examined in young (3-month), adult (8-month) and aged (26-month old) Fisher 344 rats, because age-related changes in physiology and biochemistry are well characterized in this strain of rats. Although rats are uniquely tolerant to digitalis, basic mechanisms leading to inotropic and toxic actions of digitalis are not different from other species. In aged anesthetized rats, intravenous infusion of ouabain produced arrhythmias and cardiac arrest at lower doses. Aged myocardium had lower Na,K-ATPase activity and fewer high affinity [3H]ouabain binding sites. Affinity of the ouabain binding sites on Na,K-ATPase was not altered. Despite these findings, sodium pump activity, estimated from the ouabain-sensitive 86Rb+ uptake by ventricular muscle slices, was higher in the aged myocardium when the uptake was observed in the absence of ouabain and was more sensitive to inhibitory action of the glycoside. Differences in Na,K-ATPase and sodium pump data may be explained if sodium leak influx is increased in aged myocardium. Fewer sodium pumping sites and enhanced ouabain sensitivity of the sodium pump seem to be responsible for the reduced tolerance of aged heart to digitalis-induced toxicity.