INOTROPIC SYNERGISM OF CARDIAC GLUCOSIDE WITH CALCIUM ACTING ON THE FROG'S HEART IN ARTIFICIAL MEDIA

¹ Laboratories of Pharmacology and Toxicology, Yale University School of Medicine, New Haven, Connecticut

The isolated frog heart responds to concentrations of hydrated ouabain about 5 micrograms per cent (i.e., 0.0001 millimolar) in Locke's solution. Thus p [Ouabain] is about 7 in the inotropic range, like pH and p [Thiamine]. When the isotonic contraction of the heart is depressed by lowering the concentration of calcium ions, the contractile response may be restored by adding ouabain or digitoxin. This synergism follows simple linear functions relating k [G] to [Ca⁺⁺₅₀], where k is the relative potency of the drug and [G] the concentration of the drug. This technical approach can be applied to other cardiac drugs; so that potency is measured in terms of the number of calcium ions for which each molecule of drug can compensate.