Influence of frequency of stimulation on the toxicity of digoxin on isolated guinea-pig atria in different extracellular Ca2+.

In isolated guinea-pig left atria driven by rates of 0.5, 1,2, 3 and 4 Hz digoxin was infused continuously until cardiac arrest occurred. The experiments were performed in Tyrode solution with normal and twice the calcium content. Calculated was the toxic concentration of digoxin as that concentration which caused arrest of the preparation. In normal Ca2+-content (1.8 mM) an increase of the driving frequency decreased significantly the toxic concentration of digoxin, i.e. elevated the toxicity of this cardiac glycoside. The elevation of the Ca2+-content of the Tyrode caused a further diminution of the toxic concentrations of digoxin in dependence of the driving rate, thus demonstrating a synergism of Ca2+ and digoxin with regard to its toxicity.