Erythrocyte sodium/potassium ATPase activity in severe preeclampsia

Adair, Charles; Haupert, Garner T.; Koh, Ho‐Jin; Wang, Y.; Veille, Jean Claude; Buckalew, Vardaman M.

doi:10.1038/jp.2008.223

Cited by 11 publications

(12 citation statements)

References 39 publications

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“…In confirmation of previous studies, 36 we demonstrated sodium pump inhibitory activity in serum of severe preeclamptic patients. Moreover, pump inhibitory activity decreased in the group given DIF, suggesting that DIF, as hypothesized, bound and neutralized EDLF.…”

Section: Discussionsupporting

confidence: 92%

Digoxin Immune Fab Treatment for Severe Preeclampsia

et al. 2010

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We evaluated the efficacy, safety, and biological mechanisms of digoxin immune Fab (DIF) treatment of severe preeclampsia. Fifty-one severe preeclamptic patients were randomized in double-blind fashion to DIF ( N = 24) or placebo ( N = 27) for 48 hours. Primary outcomes were change in creatinine clearance (CrCl) at 24 to 48 hours and antihypertensive drug use. Serum sodium pump inhibition, a sequela of endogenous digitalis-like factors (EDLF), was also assessed. CrCl in DIF subjects was essentially unchanged from baseline versus a decrease with placebo (-3 +/- 10 and -34 +/- 10 mL/min, respectively, P = 0.02). Antihypertensive use was similar between treatments (46 and 52%, respectively, P = 0.7). Serum sodium pump inhibition was decreased with DIF compared with placebo at 24 hours after treatment initiation (least squares mean difference, 19 percentage points, P = 0.03). DIF appeared to be well tolerated. These results suggest DIF prevents a decline in renal function in severe preeclampsia by neutralizing EDLF. Sodium pump inhibition was significantly improved. Further research is warranted.

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Section: Discussionsupporting

confidence: 92%

Digoxin Immune Fab Treatment for Severe Preeclampsia

et al. 2010

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“…Moreover, it has also been observed that the Na/K-ATPase from preeclamptic placentae exhibited heightened sensitivity to CTS [21]. The mechanism underlying the antihypertensive effects of Digibind is based on the cross-reactivity with endogenous CTS; this is illustrated by several observations including the restoration of erythrocyte Na/K-ATPase activity by Digibind ex vivo [13,14] and the reduction in plasma Na/K-ATPase inhibitory activity following Digibind infusion [22]. Accordingly, in pregnant, NaCl-supplemented rats which exhibit symptoms of preeclampsia, the antihypertensive effects of Digibind as well as of anti-MBG mAb were associated with the restoration of vascular and erythrocyte Na/K-ATPase [14].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae

Федорова

Tapilskaya²,

Bzhelyansky

et al. 2010

Journal of Hypertension

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Background-Preeclampsia (PE) is a major cause of maternal and fetal mortality, and its pathogenesis is not fully understood. Endogenous digitalis-like cardiotonic steroids (CTS) have been implicated in the pathophysiology of PE; this is illustrated by clinical observations that Digibind, a therapeutic digoxin antibody fragment which binds CTS, lowers blood pressure and reverses Na/KATPase inhibition in patients with PE. Recently we reported that plasma levels of marinobufagenin (MBG), a bufadienolide vasoconstrictor CTS, are increased four-fold in patients with severe PE.

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“…The antihypertensive activity of Digibind is based on the binding of CTS and reversal of the vasoconstriction. Thus, administration of Digibind to patients with PE is associated with restoration of activity of erythrocyte Na/K-ATPase, a target enzyme for CTS (19). Accordingly, ex vivo anti-MBG mAb and Digibind also restore PE-induced inhibition of erythrocyte Na/K-ATPase (6,7).…”

Section: Introductionmentioning

confidence: 99%

DigiFab Interacts With Endogenous Cardiotonic Steroids and Reverses Preeclampsia-Induced Na/K-ATPase Inhibition

Ishkaraeva-Yakovleva¹,

Федорова

Солодовникова³

et al. 2012

Reprod. Sci.

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Elevated levels of endogenous Na/K-ATPase (NKA) inhibitors, cardiotonic steroids (CTS) including marinobufagenin (MBG), contribute to pathogenesis of preeclampsia (PE) and represent a target for immunoneutralization by Digibind (Ovine Digoxin Immune Antibody, Glaxo-Smith Kline). Because Digibind is no longer commercially available we studied whether DigiFab (BTG International Ltd, UK) can substitute Digibind for immunoneutralization of CTS in patients with PE. We compared DigiFab, Digibind and anti-MBG monoclonal antibody (mAb) with respect to their ability to interact with CTS in PE plasma and to restore NKA activity in erythrocytes from patients with PE. Using immunoassays based on DigiFab, Digibind, and anti-MBG mAb we studied the elution profile of CTS following HPLC-fractionation of PE plasma. Seven patients with mild PE (28±2 years; gestational age, 39±0.5 weeks; blood pressure 156±5/94±2 mmHg) and six normotensive pregnant subjects (28±1 years; gestational age, 39±0.4 weeks; blood pressure 111±2/73±2 mmHg) were enrolled. PE was associated with a substantial inhibition of erythrocyte NKA (1.47±0.17 vs. 2.65±0.16 μmol Pi/mL/hr in control group, P<0.001). Ex vivo, at concentration 10 μg/mL, which is consistent with the clinical dosing of Digibind administered previously in PE, DigiFab and Digibind as well as anti-MBG mAb (0.5 μg/mL) restored erythrocyte NKA activity. Following HPLC fractionation of pooled PE and control plasma, PE-associated increase in CTS material was detected by Digibind (176 vs. 75 pmoles), DigiFab (221 vs. 70 pmoles) and anti-MBG mAb (1056 vs. 421 pmoles). Therefore, because DigiFab interacts with CTS from PE plasma and reverses PE-induced NKA inhibition, it can substitute Digibind for immunoneutralization of CTS in patients with PE.

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Erythrocyte sodium/potassium ATPase activity in severe preeclampsia

Cited by 11 publications

References 39 publications

Digoxin Immune Fab Treatment for Severe Preeclampsia

Digoxin Immune Fab Treatment for Severe Preeclampsia

Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae

DigiFab Interacts With Endogenous Cardiotonic Steroids and Reverses Preeclampsia-Induced Na/K-ATPase Inhibition

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