In vivo assessment of the inotropic and toxic effects of oxidized ouabain

Oxidized ouabain, a product of the oxidative cleavage of the rhamnose ring in ouabain has been found to have a higher inotropic toxic ratio in cultured cardiac myocytes. The purpose of our study was to evaluate the efficacy and toxicity of oxidized ouabain in comparison with ouabain in intact animals. Drugs were infused to healthy cats; the positive inotropic effect, and the time-course of development of arrhythmia were followed and recorded until death. Oxidized ouabain was associated with a higher increase in arterial blood pressure, a mean increase of 41 +/- 19% as compared with 21 +/- 8% in the ouabain group (p < 0.10). There were no significant differences in maximal increases of dP/dt or dP/dt/P (65 +/- 29%, 28 +/- 10% for oxidized ouabain and 49 +/- 16%, 27 +/- 11% for ouabain, respectively). The mean doses causing persistent arrhythmia (toxic dose) were 93 +/- 23 micrograms/kg of oxidized ouabain vs 39 +/- 14 micrograms/kg of ouabain. Lethal arrhythmias were produced by 215 +/- 46 micrograms/kg of oxidized ouabain and 62 +/- 16 micrograms/kg of ouabain. The ratio of toxic to lethal doses was 0.62 +/- 0.11 for ouabain vs 0.45 +/- 0.09 for oxidized ouabain (p < 0.05), but the inotropic to toxic dose ratios were not different. We conclude that oxidized ouabain acts similarly to the known cardiac glycosides in doses which produce inotropic effects in cats, has a lower potency as compared to ouabain, and appears to have a more benign course of intoxication.