Accumulation of 3H-digitoxin in CNS of cats with a hypersensitivity to the drug.

Considerable literature (1-6) is available on "the cumulative effect of digitalis", but the mechanism involved in the appearance of this "cumulative effect" is still a matter of speculation. Previous reports suggest the possibility that cardiac glycosides may produce their effects on the heart through the central nervous system (CNS) (7, 8). The present work was designed to determine whether "the cumulative effect of digitalis" occurs as a result of the central accumulation of digitalis or is due to the cardiac accumulation of the drug. The experiment was carried out using cats. At both one and 48 hours after a single injection (17 lcci/132 jig/kg) of 3H-digitoxin (New England Nuclear Corp., S.A.: 26 mci/mg), the following procedures were carried out; 1) determination of both arrhythmic and lethal doses of digitoxin by Hatcher's method, 2) measurement of glycoside (digitoxin and its metabolites) content in the medulla, midbrain, heart, kidney and liver by means of the combustion method (Tri-Carb sample oxidizer, Packard Model 305). Radioactivity was determined using a liquid scintillation spectrometer. CHC13 soluble extracts were separated by a thin layer chromatographic technique after a CHCl3-extraction from the homogenate of the each tissue. At 48 hours after the injection, both arrhythmic dose (190±25 Iug/kg) and lethal dose (317±33 ,ug/kg) of digitoxin were decreased to one half of each control value (arrhythmic dose; 423+45 ,ug/kg, lethal dose; 660±43 'ug/kg). At one hour after the injection, both arrhythmic and lethal doses were found to be much the same as the control values. Forty eight hours after the injection of digitoxin, a marked hypersensitivity to the drug was seen