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SUMMARY We studied the effects of sustained subtoxic doses of ouabain on left ventricular myocardial monovalent cation active transport and contractility in open-chest dogs. Using a serial biopsy technique, full-thickness left ventricular myocardial samples were obtained prior to and 1 and 2 hours after ouabain infusion, according to a loading dose and infusion schedule demonstrated to produce stable plasma and left ventricular myocardial ouabain concentrations. Ouabain-inhibitable uptake of the potassium analogue86Rb+ was measured in vitro in these biopsy samples and compared with transport activity in biopsies taken prior to ouabain administration and values in biopsies from dogs receiving vehicle alone. Left ventricular maximum dP/dt increased above baseline values by 29 ± 3 = % (SKM) and 46 ± 9% in ouabain-treated dogs at the 1- and 2-hour biopsy times, respectively, and active transport of86Rb+ was significantly reduced by 21 ± 6% at 1 hour and 33 ± 5% at 2 hours. Continuous ECG monitoring did not show any arrhythmias. Control dogs receiving vehicle alone had unchanged values for contractility and monovalent cation transport. In another group of dogs, significant inhibition of active ""Rb+transport was demonstrated at the time a sustained ouabain-induced positive inotropic effect was first clearly demonstrable (30 minutes). In contrast, norepinephrine in doses sufficient to produce comparable increases in dP/dt for 30-120 minutes did not change active80Rb+ transport. These results demonstrate that subtoxic doses of ouabain sufficient to induce a positive inotropic effect are associated with significant reduction of myocardial monovalent cation active transport in a cardiac glycoside-sensitive species. Although a causal relationship cannot be established on the basis of these data, our findings are consistent with the hypothesis that cardiac glycoside-induced inotropy is related to inhibition of myocardial NaK-ATPase-mediated monovalent cation transport.

Inhibition of myocardial monovalent cation active transport by subtoxic doses of ouabain in the dog.