On the mechanism of the positive inotropy of low concentrations of strophanthidin.

The hypothesis that low concentrations of strophanthidin may decrease contractile force (and intracellular sodium activity, aiNa) under normal conditions but might increase force (while still decreasing aiNa) under conditions of increased Ca load was tested in sheep cardiac Purkinje fibers perfused in vitro. Strophanthidin was used at concentrations (7.5-25 nM, "low strophanthidin") that decreased both force and aiNa in different preparations. A marked reduction in flow rate of Tyrode solution ("ischemia") increases aiNa and increases and eventually decreases force: during ischemia, low strophanthidin decreases aiNa but increases force. High [Ca]o (16.2 mM) and norepinephrine (10 nM) increase force and decrease aiNa: in their presence, low strophanthidin decreases aiNa further but increases force. Caffeine (4 mM) decreases force and increases aiNa, and low strophanthidin increases force while having little effect on the increase of aiNa. In ventricular trabeculae, strophanthidin decreases force under basal conditions but increases force during ischemia or Ca overload. Thus, strophanthidin decreases force by lowering aiNa under normal conditions, but it increases force in spite (and perhaps because) of the decrease in aina under conditions of increased calcium load.