Myocardial ouabain content and susceptibility to ouabain cardiotoxicity associated with circulatory volume overload in the dog.

The influence of circulatory volume overload on the myocardial uptake of ouabain and on cardiotoxicity was studied in the unanaesthetised dog with aorto-caval fistula. One hour after tritiated ouabain (0-02 mg/kg IV) 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 less than 0-001) while concentrations in skeletal muscle, liver, kidney and plasma were not different in the two groups. In other experiments ouabain was infused to cardiotoxicity (7-5 microgram/kg followed by 3 microgram/kg/min). Cardiotoxicity occurred earlier in dogs with fistula than in normals (16-5+/-2-7 min vs. 24-1+/-2-4 min, P less than 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 less than 0-001; 1422+/-189 ng/g vs. 2747+/-479 ng/g, P less than 0-001). Average content of skeletal muscle was also less, in proportion to administered dose. The increment in myicardial ouabain content associated with aorto-caval fistula appears to be physiologically active and hence is presumably specifically bound to the digitalis receptor. The observations in this model suggest the possibility of augmented cardiac glycoside uptake in some clinical cardiac diseases.