INTRACELLULAR DISTRIBUTION OF DIGOXIN-H3 IN THE HEARTS OF RATS AND DOGS DEMONSTRATED BY AUTORADIOGRAPHY AND ITS RELATIONSHIP TO CHANGES IN MYOCARDIAL CONTRACTILE FORCE

¹ Department of Medicine, University of Oklahoma Medical Center, and the Medical and Research Services, Veterans Administration Hospital, Oklahoma City, Oklahoma

Tritiated digoxin was administered ultravenously in nontoxic doses to 5 anesthetized, open-chest dogs and in each serial biopsies of the left ventricle were Performed. The presence and distribution of the digoxin or its metabolites in the heart were identified by preparing autoradiographs of the biopsy specimens. Care was taken to avoid diffusion of the isotope during the procedure and to minimize background grain. Saran-coated autoradiographs showed lack of diffusion and ruled out chemical interaction between tissue and emulsion during exposure.

Examination of the autoradiographs was performed with the light microscope and the findings were confirmed with phase and polarized light. At 10 minutes the first silver grains were visible, being distributed along the myofibrils. The number of grains increased to a maximum in 2 hours. At this time they were distributed transversely across the cell in the A-band in greatest concentration although some were seen along the cell borders. At 4 hours the number of grains had decreased greatly. They were barely visible along the myofibrils at this time but were seen in greater number around the nucleus. The number of grains identified in the sarcoplasm of the heart cell correlated reasonably well with the changes in myocardial contractility produced by the administered digoxin.

The cumulative and/or higher dose effects of repeated digoxin-H³ administration over a 2- week interval were observed in 2 rats. Auto-radiographs of the hearts of these animals showed clearly the tritium label to be localized to the A- hand and, to a lesser extent, to the cell membrane.