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

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.