Enhanced sensitivity to digoxin in dystrophic mice.
We estimated the effect of digoxin on the myocardial potassium content and the action potentials of the left ventricular papillary muscles in dystrophic mice (C57BL/6JCL dy X dy). All of 10 dystrophic mice died following ip injection of digoxin at a dose of one quarter of the iv LD50 for normal mice. The myocardial digoxin concentration and the myocardial potassium content in dystrophic mice were similar to those in normal mice before and 60 min after the ip injection of digoxin. The action potential durations (APD) in dystrophic mice were significantly longer than those in normal mice. Perfusion of digoxin (2 micrograms/ml) for 30 min reduced the APD significantly and induced arrhythmias in dystrophic mice, but it did not bring about any significant change in normal mice. These data suggest that dystrophic mice have increased sensitivity to digitalis. This hypersensitivity to digitalis is not due to increased myocardial digoxin uptake or decreased myocardial potassium content.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004077:Digoxin / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium