Pharmacodynamic effects of ouabain following single sublingual and intravenous doses in normal subjects

Summary

In this intraindividual, placebo-controlled, double blind study the dynamic effects of single doses of ouabain 0.5 mg i.v. and 12 mg sublingual were compared with those of the vasodilator sublingual nitroglycerin 0.8 mg. In 12 (sublingual) and 6 (i.v.) healthy volunteers, respectively, cardiac performance was assessed for 60 min after administration, using systolic time intervals (QS₂c, PEPc, PEP/LVET), electrical impedance cardiography ((dZ/dt)/RZ index) and echocardiography (EDD, ESD, FS). After i.v. ouabain the typical positive inotropic glycoside effects appeared (shortening of QS₂c, PEPc, and PEP/LVET, increase of (dZ/dt)/RZ and FS, decrease of EDD and ESD). With nitroglycerin preload reduction diminished cardiac performance, as shown by a rise in PEPc and PEP/LVET and depression of (dZ/dt)/RZ. In addition, EDD (not significant) and ESD were somewhat reduced, FS was enhanced, and QS₂c tended to shorten. Following sublingual ouabain, QS₂c was unchanged, there was an increase in PEPc and PEP/LVET, a decrease in (dZ/dt)/RZ and FS, EDD was unchanged, and ESD rose. By this route the absolute magnitude of the effects was about 1/3 that of the i.v. drug action. The spectrum of effects of sublingual ouabain indicates a reduction in cardiac performance without any detectable inotropic action. The effects seem to be induced by load changes, with an indication of an increase in afterload although an additional preload reduction cannot be excluded. This dose of the drug given by the sublingual route appears, therefore, to alter cardiac function via an effect on the peripheral circulation, although the final mechanism has not yet been elucidated. It is not known whether these biological effects in healthy subjects may have any clinical significance in patients with cardiac disorders.