Cardiac hypertrophy determines digitalis action on intracellular Ca²⁺ in human myocardium

Ventricular hypertrophy alters transporters associated with digitalis action, but the outcome of digitalis treatment on intracellular cations in the hypertrophied human myocardium remains unknown. Using double-barreled Ca²⁺-selective microelectrodes, we simultaneously measured Ca²⁺ activity and membrane potential in myocardial samples from patients without and with ventricular hypertrophy, prior to and following exposure to strophanthidin, a prototype digitalis. We found that ventricular hypertrophy is associated with greater strophanthidin-induced increase in diastolic Ca²⁺ levels compared to that observed in the absence of hypertrophy. Furthermore, in hypertrophied myocardium the magnitude of the increase in Ca²⁺ induced by strophanthidin was inversely related to increase in myocardial mass. Thus, the extent of ventricular hypertrophy determines digitalis action on intracellular Ca²⁺ within the human myocardium.