Direct Evidence for the Intimate Relationship between the Uptake of Digitoxin and an Activity of Guinea Pig Heart.

" ¡–ì • ŸŽq • E 'åŽ-‰p • ¢ • E Ž • " c —S • G • E " c' † OEì Though the view, that there would be an intimate relationship between the cardiac action of digitalis glycosides and the uptake of the drugs by heart, has been often regarded as a well established basis in understanding of the mechanism in the cardiac action of the drugs (1, 2), direct evidence for its validity is not yet given. The present communication is concerned with the direct demonstration of this evidence and shows a highly intimate relationship between the uptake of digitoxin and the cessation of beating in guinea pig heart. FiG. 1. The relationship between the cessation of beating and the uptake of digitoxin in guinea pig ventricle of heart under the various concentrations of potas sium. Symbols of a, b, and c repre sent the cases of the perfusion with digitoxin solutions under the conditions of normal concen tration, 2.8 mm, and 8.4 mm of potassium, respectively. The de termination of content of digi toxin in heart ventricle was done by the method of Repke (7). Each value is the mean based on 10 determinations, and horizontal bars in C indicate standard error of the mean. Upon the addition of digitoxin of 2 x 10-7 g/ml, the automatically driven guinea pig heart stops beating in 100 min under the condition of normal Ringer-Locke solution (a) and in 40 min under the potassium-deficient condition (b), whereas under the potassium-rich condition the heart continues to beat even in 250 min (c), as is shown in Fig. 1-A. At the time of cessation of beating, no response to electric shock given was detected. These mechanical and electrocardiographical results as such are not new ; and such phenomena have been already reported (3-6). It is, however, very noteworthy that, when the uptake of digitoxin by heart is determined at the time of the cessation of beating, a new relationship on the cardiac action of digitoxin is recognizable : As is shown in columns a and b of Fig. 1-C, the uptake of digitoxin upon the cessation of beating is strikingly similar between upto the normal condition and under the potassium deficient one, in spite of the considerably marked dif ference between their total volumes of perfusion fluid (Fig. 1-B). In accord with this intimate relationship, the column c of Fig. …