Abstract
The influence of heart rate on the action of ouabain on contraction and calcium (Ca) exchange in guinea pig atria has been examined. Concentrations of the drug producing a therapeutic effect (positive inotropic effect) at a given frequency became progressively more toxic (arrhythmias, negative inotropic effect) as the rate of beat increased. Paralleling these changes, one noted a progressively increasing effect of the drug to enhance Ca exchange. When contractures occurred, a rise in tissue Ca was observed. It was concluded that the therapeutic effect of ouabain results from a further mobilization of tissue Ca that occurs with each heartbeat. It was suggested that when the rate of mobilization of tissue Ca by the drug exceeded a critical value, toxic manifestations appear. Thus, it would seem from the data that the basic mechanism of the therapeutic and toxic effects of ouabain are but an expression of varying degrees of the same chain of physicochemical events: namely varying degrees of effect on Ca exchange in the myocardium.
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