Age dependence of myocardial Na+-K+-ATPase activity and digitalis intoxication in the dog and guinea pig.

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Abstract
Infants and young animals tolerate higher doses of digitalis glycosides, relative to body weight, than adults. One possible explanation for this could be an age-dependent difference in the myocardial digitalis receptor, the Na+-K+-ATPase. Two functions of this enzyme were studied in adult, 1- and 6-week-old dogs and guinea pigs: in vitro myocardial uptake of rubidium (86Rb) and binding of ouabain. In guinea pigs, rubidium uptake (pmol Rb/mg LV per 15 min) was: 1 week old: 100.9 +/- 7.1 (mean +/- SE); 6 week: 79.8 +/- 6.7 adult: 55.2 +/- 7.9; (1 week: 6 week: P less than 0.025; 1 week: adult, P less than 0.001; 6 week: adult, P less than 0.025). Similarly in dogs, rubidium uptake was significantly greater at 1 week than at 6 weeks (208 +/- 13 vs. 144 +/- 9; P less than 0.001) and the latter greater than in adults (111 +/- 4) (P less than 0.005). Other groups of anesthetized adult and 6-week-old dogs were given digoxin, 0.3 mg/kg, iv. The young dogs took significantly longer to become cardiotoxic (17.3 +/- 3.4 min vs. 9.3 +/- 1.4 min; P less than 0.025), while their myocardial digoxin uptake was at least as great. Rubidium uptake showed an average decrease of 56% after digoxin but residual uptakes were not different in the two groups. Data for ouabain binding showed similar differences between the various groups of dogs studied. Increased myocardial Na+-K+-ATPase activity, reflected in greater active cation transport and specific enzyme binding, has been demonstrated in young animals and may be partly responsible for their greater tolerance to digitalis glycosides.