Infusion Rate-Dependent Positive Inotropic Action of Ouabain in Rabbits

The effect of the infusion rate on the relationship between plasma concentration (Cp) and positive inotropic action (PIA) of ouabain was studied in rabbits. The maximum of the first derivative of the left ventricular pressure (dP/dtmax) was used as an index of PIA. The Cp of ouabain was measured by counting the radioactivity of 3H-ouabain, a nonmetabolizable cardiac glycoside. 3H-Ouabain was infused via the femoral vein at 2.7, 13 and 38 nmol/min/kg, and the time courses of Cp and dP/dtmax were measured simultaneously. Non-linear initial volume of distribution was suggested from the different slopes of the Cp curves normalized by infusion rate during the initial 5 min. The relationship between Cp and PIA depended remarkably on the infusion rate. The values of Cp which produced the maximum PIA at the low, medium and high infusion rates were 136± 18, 700 ± 210 and 2300 ± 545 nM (mean ± S.E.M.), respectively. The total amounts of infused ouabain until the maximum PIA at the low, medium and high infusion rates were 81 ± 6.8, 130± 6.5 and 152 ± 7.2 nmol/kg (mean ± S.E.M.), respectively. It was clear that ouabain does not exhibit its action in the central compartment, although it is considered to be a fast-acting cardiac glycoside. It is suggested that a slow step exists in the appearance of PIA of ouabain in rabbits.