How does digoxin primarily enhance contractility in heart failure?

Digoxin primarily enhances contractility in heart failure by increasing intracellular sodium levels. This occurs through its action as an inhibitor of the Na+/K+ ATPase pump, which leads to an accumulation of sodium ions inside the cardiac myocytes.

As intracellular sodium levels rise, the gradient for the Na+/Ca2+ exchanger is altered. Under normal circumstances, sodium influx results in the efflux of calcium from the cell. However, with increased sodium concentration, the activity of this exchanger is reduced, leading to decreased calcium extrusion. Consequently, more calcium remains inside the cell, which enhances calcium's availability for contraction, thereby leading to increased contractility of the heart muscle.

This mechanism is central to the clinical application of digoxin in treating heart failure, as it improves cardiac output and helps alleviate symptoms associated with reduced myocardial contractility.