Digoxin's Minimal Inotropic Effect Is Not Limited by Sodium—Calcium Exchange in the Intact Immature Rabbit Heart

Abstract

Background: In the intact immature heart, how much digoxin can drive sodium-calcium exchange has not been studied in the context of sodium-calcium exchanger abundance. Methods and Results: The effects of digoxin and low potassium on contractility in the intact, paced and isovolumically contracting immature rabbit heart were studied in both the absence and presence of L-type calcium channel blockade. Without calcium channel block ade, digoxin increased contractility minimally and only at 10^-6 M/L. In contrast, low potas sium (2.2 mM/L) substantially increased contractility in all experiments, a result indicating abundant sodium-calcium exchanger activity. During nifedipine-induced calcium channel blockade, digoxin (10^-6 M/L) allowed modest recovery of contractility, whereas digoxin and low potassium together allowed complete recovery as assessed by dP/dt_max; however, all hearts so perfused subsequently developed ventricular fibrillation, presumably because of calcium overload.

Conclusions: In intact immature rabbit heart, digoxin can drive sodium-calcium exchange and thus increase contractility to only a minimal extent. This effect does not appear to be lim ited by intrinsic exchanger activity, which appears abundant in this preparation. Rather, digoxin's inability to drive the sodium-calcium exchanger may be due to developmental dif ferences in binding to the sodium pump. The sodium-calcium exchanger itself seems capable not only of providing enough intracellular calcium for normal contraction, but also of over loading the myocardium with calcium, despite L-type calcium channel blockade.