Myocardial Ouabain Content and Susceptibility to Ouabain Cardiotoxicity Associated with Circulatory Volume Overload in the Dog*

Abstract

The influence of circulatory volume overload on the myocardial uptake of ouabain and on cardiotoxicity was studied in the unanaesthetized dog with aorto-caval fistula. One h after tritiated ouabain (0.02 mg/kg i.v.) both ventricles and atria contained more ouabain than did those of normal dogs (left ventricle (LV), 166 .+-. 23 (SD) ng/g vs. 97 .+-. 19 ng/g, P < 0.001) while concentrations in skeletal muscle, liver, kidney and plasma were not different in the 2 groups. In other experiments, ouabain was infused to cardiotoxicity (7.5 .mu.g/kg followed by 3 .mu.g/kg per min). Cardiotoxicity occurred earlier in dogs with fistula than in normals (16.5 .+-. 2.7 min vs. 24.1 .+-. 2.4 min, P < 0.001). Ouabain concentrations in myocardium were not different (LV, 434 .+-. 58 ng/g, vs. 442 .+-. 42 ng/g) while concentrations in liver and kidney were less in those with fistula (181 .+-. 35 ng/g vs. 278 .+-. 69 ng/g, P < 0.001; 1422 .+-. 189 ng/g vs. 2747 .+-. 479 ng/g, P < 0.001). Average content of skeletal muscle was also less, in proportion to administered dose. The increment in myocardial ouabain content associated with aorto-caval fistula appears to be physiologically active and is presumably specifically bound to the digitalis receptor. The observations in this model suggest the possibility of augmented cardiac glycoside uptake in some clinical [human] cardiac diseases.