Elevated concentrations of endogenous ouabain in patients with congestive heart failure.

Abstract

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 less than 0.05 versus control subjects). The ouabain concentration correlated inversely with both cardiac index (r = -0.62, p less than 0.005) and mean arterial pressure (r = -0.51, p less than 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.

The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation

“…Although several studies have shown a correlation between elevated endogenous cardiac glycosides and certain pathological conditions, the physiological function of endogenous cardiac glycoside-like compounds is still uncertain (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17).…”

“…Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17). In addition, marked increases in endogenous ouabain-like compounds occur in congestive heart failure, both in animal models and human patients (18)(19)(20). One concern raised with respect to endogenous cardiac glycoside-like compounds is that they occur in levels which may not significantly inhibit the Na,K-ATPase.…”

A hearty solution for acute myeloid leukemia

“…Second, the activity of ouabain on Na/K ATPase might be dose-dependent. Since endogenous ouabain-like substance is also present in human body at pico-tonanomolar ranges, suggesting that the level of endogenous ouabain in leukemic patients might be too low to affect NF-κB and that frequent infusion of exogenous ouabain to maintain plasma concentration high enough might be needed to sustain the inhibition of NF-κB [14,15] . If so, systemic toxicity might be the limiting factor for its use especially in the elderly patients which constitute the bulk of leukemic patients.…”

The sodium pump and hypertension: A physiological role for the cardiac glycoside binding site of the Na,K-ATPase

“…The identification of cardiac glycoside-like molecules in mammals has led to the proposal that these compounds are natural regulators of Na,K-ATPase in vivo (7)(8)(9)(10). Several studies have shown a correlation between these cardiac glycoside-like molecules and certain pathological conditions, such as hypertension and heart failure (11)(12)(13)(14)(15)(16)(17). Plasma levels of these putative ligands for the Na,KATPase are high in several animal hypertension models, as well as in human essential hypertension and preeclampsia (11-14, 18, 19).…”

“…Plasma levels of these putative ligands for the Na,KATPase are high in several animal hypertension models, as well as in human essential hypertension and preeclampsia (11-14, 18, 19). In addition, marked increases in peripheral and central endogenous ouabain-like compounds occur in animal models of congestive heart failure as well as in human patients (15)(16)(17). However, it is still difficult to draw definitive conclusions regarding the specific function of these molecules in pathophysiology.…”