Digitalis glycosides mechanical effects

Digitalis glycosides enhance the inotropic state by increasing the intracellular calcium concentration. Intracellular calcium overload is also the mechanism for proarrhythmia associated with digitalis intoxication. The direct effect of digitalis on the electrophysiology of the myocytes is to increase the slope of phase 4 depolarization, an effect that enhances automaticity. 

To better understand certain aspects of the mechanism of digitalis drugs, it would be useful to outline briefly their cardiovascular properties. The increased force of myocardial contraction produced by these glycosides is by far their most dramatic pharmacodynamic property. This positive inotropic (increased contractile force) action translates into increased cardiac output and effects on cardiac size and blood volume through diuresis (i.e., the relief of the edema that accompanies CHF). The rate of tension development is apparently affected, not the length of time during which contraction is maintained by the muscle fiber. Digitalis exerts its effect even in the presence of p-blockers or reserpine. 

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