Distribution of digoxin in the human heart.

DATA defining the intramyocardial distribution of digoxin and its relationship to serum levels are lacking primarily owing to the limitation of an adequate supply of myocardial tissue for study. By using the recipient heart removed at the time of cardiac transplantation a supply of myocardial tissue is realized for more definitive studies of the distribution of digoxin, as reported in this study. Although the cardiac receptors which mediate the pharmacological effect of the cardiac glycosides have neither been fully isolated nor fully identified, evidence suggests that the sodium potassium-activated adenosine triphosphatase, (Na+, K+)-ATPase, plays a role in the mechanism of action of the cardiac glycosides (Akera, Larsen and Brody, 1970; Besch et al., 1970). In this study, we have identified this enzyme in a microsomal fraction of the heart and measured the activity of the enzyme in vivo and to varying concentration of digoxin in vitro. Furthermore, patients undergoing transplantation in this study had end-stage cardiac disease due either to severe ischaemic heart disease or cardiomyopathy; we have, therefore, correlated the effects of cardiac histology with the distribution of digoxin in the various chambers of the heart, both on a subcellular and enzymatic level.