Abstract

Isolated guinea pig hearts were perfused with digitoxin-C14. The treated hearts were differentially centrifuged into contaminated-nuclear, debris, mitochondria and aqueous fractions.

The greatest amount of radioactivity was found in the aqueous fraction; however, at 37°C. most of this activity was in the intravascular space. When the vascular space was washed free of radioactive perfusion medium, the debris fraction contained the greatest and the nuclear fraction the second greatest amount of radioactivity. Under these conditions the mitochondria and aqueous fractions each contained less than one-fourth as much as the debris fraction. The highest concentration of radioactivity was found in the debris fraction and the least concentration in the aqueous fraction. The radioactivity in the nuclear fraction was not in the nuclei but rather in the contaminating debris. Any alteration in the calcium or potassium content of the perfusion medium tended to reduce the radioactivity in the particulate fractions and to elevate that in the aqueous fractions.

Calcium excess decreased, whereas calcium deficiency and potassium deficiency increased, the potency of digitoxin when amplitude rather than rhythm was employed as the dependent variable. Changes in uptake and distribution of radiodigitoxin in the nuclear fraction correlated best with changes in potency induced by alterations in calcium concentration.

At both 34° and 40°C. the uptake of radioactivity was higher than at 37°C. The greatest percentage increase occurred in the aqueous fraction, but the highest concentration remained in the debris fraction.

At both 34° and 40°C. the potency of digitoxin was higher than at 37°C. There is a correlation between potency and uptake in the several fractions, except the nuclear fraction; therefore, the correlation indicated above is difficult of interpretation.

At 37°C. the digitoxin (radioactivity) space is only slightly larger than the intravascular space and much smaller than the chloride space. Therefore, very little digitoxin must remain in the interstitial and cytoplasmic fluids. Alterations in cation composition of the medium and in temperature increase the amount of radioactivity in these fluid compartments. From these findings a transcapillary regulation of digitoxin uptake is proposed.