ELEVATED CONCENTRATIONS OF ENDOGENOUS OUABAIN IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background. An endogenous digitalis-like compound in mammals has long been postulated, but only recently has a substance indistinguishable from ouabain been identified in human plasma. Because of the potential significance of such a substance in patients with congestive heart failure, we sought to evaluate the pathophysiology of endogenous ouabain in these individuals. Methods and Results. Using an immunoassay, we determined plasma ouabain concentrations in 51 patients with heart failure and in 19 control subjects. Plasma ouabain concentrations in control subjects ranged from 0.16 to 0.77 nM (mean, 0.44+/-0.20 nM). In 19 matched heart failure patients receiving digoxin, the mean ouabain was significantly elevated at 1.59+/-2.2 nM (range, 0.17-8.76 nM, p<0.05 versus control subjects). The ouabain concentration correlated inversely with both cardiac index (r=-0.62, p<0.005) and mean arterial pressure (r=-0.51, p<0.05). However, there was no correlation between ouabain and left ventricular filling (r=0.19, NS) or right atrial pressures (r=0.20, NS). In 16 heart failure patients not receiving digoxin, the mean ouabain was 1.52+/-2.58 nM. No relation between renal function and ouabain was detected. Conclusions. The unanticipated lack of correlation of ouabain with atrial pressures indicates that volume is not the chief determinant of ouabain concentration in patients with congestive heart failure. However, the significant relations of plasma ouabain concentration with cardiac index and mean arterial pressure imply that endogenous ouabain may be an important homeostatic factor in humans.