title: Increased automaticity and decreased inotropism of ouabain in dogs with furosemide-induced hypomagnesemia.
abstract: Unusual cardiac glycoside toxicity has been reported during hypomagnesemia, but the underlying cause remains unexplained. Therefore, we characterized and compared the effects of ouabain in normo- and hypomagnesemic dogs with and without induced heart block. Hypomagnesemia (30% reduction in plasma magnesium) was induced with 7 days of furosemide treatment (20 mg/kg, p.o.). Following potassium replacement, ouabain was infused at 1 microgram/kg/min and changes in contractile force (strain gauge), electrocardiogram (ECG), ventricular automaticity, and cardiac conduction were monitored. The inotropic response, sustained ventricular arrhythmias, and death all occurred at significantly lower ouabain doses in hypomagnesemic dogs with and without heart block. The changes observed were specifically related to magnesium depletion, and not to potassium depletion. Ouabain activity was not different from control when both magnesium and potassium were replaced. Ouabain-induced increases in automaticity were enhanced during hypomagnesemia and contributed to the development of sustained ventricular arrhythmias at lower ouabain doses. Although the inotropic response occurred at smaller ouabain doses in hypomagnesemia, the overall increase in contractile force was diminished. Thus, increased glycoside toxicity appears related to enhanced automaticity development at doses which are normally subtoxic.
mesh_terms: D000818:Animals; D004285:Dogs; D005665:Furosemide / Q000009:adverse effects*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D008274:Magnesium / Q000097:blood*; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000633:toxicity*
chemical_list: D010042:Ouabain; D005665:Furosemide; D008274:Magnesium