The fundamental mechanism of inotropic action of digitalis

Evidence from several sources, including electrophysiologic studies and cation flux and content measurements, now allows a reasonably cohesive synthesis of the molecular and cellular events that lead from inhibition of the Na pump by digitalis to the enhancement of the generation of contractile force by cardiac muscle. It is generally agreed that Na pump inhibition, with consequent elevation in [Na+]i and [Ca2+]i, underlies both the therapeutic (positive inotropic) and toxic (arrhythmic) responses of the heart, and accounts for the well-known difficulty in separating therapeutic and toxic clinical effects of digitalis glycosides. In the intact patient or experimental animal, cardiac glycosides also exert effects that are mediated through neural pathways, and these can exert important influences on the integrated response to digitalis administration.