“Endogenous Digitalis” in healthy dogs and patients suffering from dilatative cardiomyopathy and atrial fibrillation

Objective: Recently, Ouabain, a water-soluble steroid and inhibitor of the sodium pump has been isolated from adrenal glands. The aim of our study was to investigate whether the endogenous cardiac glycosides Ouabain and Proscillaridin-A may act as hormones regulating circulatory function. Material and Methods: Seven healthy beagle dogs were subjected to physical exercise of 13 minutes duration running on a treadmill with a velocity of 7-8 km/h. The blood plasma immunoreactivity of the cardiac glycosides Ouabain and Proscillaridin-A as well as the lactate plasma concentration were measured at rest and just after having finished exercise. The heart frequency was recorded constantly. Furthermore, Ouabain immunoreactivity was investigated in 11 dogs suffering from dilatative cardiomyopathy associated with atrial fibrillation, lung oedema, ascites and thoracic effusion. Exclusion criterion was pretreatment of the dogs with cardiac glycosides. Results: In healthy beagle dogs, submaximal graded exercise resulted in a 487-fold, highly significant rise in Ouabain immunoreactivity (endo-Ouabain) from 14.1 +/- 5.3 nmol/l to 6882.0 +/- 1436.7 nmol/l, (p < 0.0001) and a 5-fold increase in Proscillaridin-A-immunoreactivity (9.8 +/- 2.4 nmol/l to 46.7 +/- 10.0 nmol/l, p = 0.0019) respectively. Furthermore, there was a significant elevation in the heart frequency and the lactate plasma concentration. In dogs with severe dilatative cardiomyopathy and atrial fibrillation however, endo-Ouabain was found to be significantly lower (1.5 +/- 0.4 nmol/l) than in healthy beagle dogs (p < 0.0015). Pretreatment (7 of 11 dogs) had no effect on endo-Ouabain plasma levels. Conclusions and clinical relevance: It can be concluded that physical exercise results in a rapid increase in Ouabain and Proscillaridin A-plasma levels. The extent of the rise varies, however, with the nature of the compound. Since the endo-Ouabain plasma concentrations are decreased in patients with severe cardiac failure further experiments are necessary to investigate whether a deficit of endo-Ouabain leads to cardiomyopathy in dogs and if the well known digoxin therapy is in fact acting by hormonal substitution.