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1 Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York
In the isolated or in situ myocardium the positive inotropic effect of ouabain was associated with an increased or unchanged K+ concentration while Na+ was not significantly changed. Higher concentrations of ouabain decreased tension in the isolated heart and produced irregularities in the ECG of the intact rabbit. Intracellular K+ was unchanged in the intact rabbit myocardium and decreased only after the negative inotropic effect appeared in the isolated myocardium. These results suggest that changes in contractility produced by ouabain are not related to changes in intracellular K+ or Na+ concentrations. The Hajdu hypothesis of a causal relationship between intracellular K+, Na+ and contractility is not supported by our experiments because alterations in intracellular K+ follow rather than precede the inotropic effects of ouabain. A relationship between K+ loss and the uncoupling of oxidative phosphorylation may be indicated since Lee and co-workers (1960) have reported that increased oxygen uptake also follows rather than precedes the "toxic" effects of ouabain on contractility.
Submitted on February 28, 1961