Abstract

Ouabain, 30 µg/kg, followed by infusion of 45 µg/kg/hr, was administered to anesthetized dogs seven days before and again after bilateral ureteral ligation. In nine animals (average blood urea nitrogen, 156 mg/100 ml; control plasma potassium, 6.4 mEq/l) an average of 88.7 ± 8.2 (S.E.M.) µg/kg of ouabain was required to produce arrhythmias as opposed to 50.5 ± 2.5 before ligation (P < .001). In 15 animals hemodialysis was instituted after comparable degrees of azoternia. After improvement of azotemia but maintenance of the elevated plasma potassium (average 6.0 mEq/l) in 10 animals, the toxic dose of ouabain (average 77.2 ± 3.2 µg/kg) was not significantly different from that in azotemic ones. When both azotemia and plasma potassium were corrected by hemodialysis (5 animals) the toxic dose of ouabain (average 58.0 ± 3.7 µg/kg) was not significantly different from that before ligation. Comparable acute elevations of plasma potassium by potassium infusion before ouabain administration in seven normal animals resulted in a toxic dose of ouabain (85.4 ± 6.7 µg/kg) not significantly different from that in ligated hyperpotassemic dogs. The fatal dose of ouabain was increased only slightly in hyperpotassemic animals: the toxic dose comprised 93.5% of the fatal dose in the azotemic hyperpotassemic dogs. In ligated animals ouabain produced a marked increase in plasma potassium. These results suggest: 1) the development of glycosido-induced arrhythmias in the presence of renal failure is influenced primarily by concomitant changes in potassium homeostasis when the effect of renal disease on glycoside excretion is excluded; 2) in the presence of limited renal excretion the glycosides may produce a hazardous rise in plasma potassium; and 3) under these conditions the difference between toxic and fatal dose of the glycosides may be small.