[Assay of cardiotonic steroids based on a 2-compartment model]

In an attempt to develop an assay method for cardiotonic steroids (CS), a two compartment model was applied to the whole dog. As representative CS, g-strophanthin, digoxin and digoxigenin were infused continuously to the animal, and the minimal cardiotonic, irregularity and lethal doses were determined, together with indices K1 and K2, representing the rate of uptake and elimination, respectively, of these compounds into and out of a specific site within the myocardium. The order of cardiotonic potency was: g-strophanthin greater than digoxin greater than digoxigenin. The indices K1 (and K2) were the greatest with digoxigenin )digoxigenin), the second greatest with g-strophanthin (digoxin) and the smallest with digoxin (g-strophanthin). The order of the margin of safety as a ratio between the minimal irregularity and the minimal cardiotonic doses was: digoxin greather than g-strrophanthin greather than lethal and the minimal cardiotonic doses. The cardiotonic, irregularity and lethal doses obtained in the present study coincided well with the values obtained in the canine heart-lung preparations, thus lending further support to the idea that effects of the CS appear when the substances accumulated to a definite amount at a specific site within the myocardium.