Сardiotonic steroids neutralization as a therapeutic approach in preeclampsia

В. В. Ишкараева¹, Н. Г. Солодовникова¹, И. Е. Зазерская¹, В. Е. Фролова², О. В. Фёдорова³, А. Я. Багров³

Authors: V. V. Ishkaraeva 1, N. G. Solodovnikova 1, I. E. Zazerskaya 1, E. V. Frolova 2, O. V. Fedorova 3, A. Y. Bagrov 3

Place: St Petersburg, Russia
Baltimore, Maryland, United States of America

Institution:
1 Institute of Perinatology and Pediatrics, Federal North-West Medical Research Centre, St Petersburg, Russia
2 Laboratory of Pharmacology, Sechenov Institute of Evolutionary Physiology and Biochemistry, St Petersburg, Russia
3 Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America

Abstract: Preeclampsia (PE) is a serious complication of late pregnancy. objective. To study and to explore the possibilities of neutralization of cardiotonic steroids, to define the possible mechanisms of recovery activity Na/K-ATPase in pregnant women with PE for the prevention of vasospasm. Design and methods. The study was carried out in two stages. Firstly, two groups of pregnant women were included. Control group consisted of 6 women with normal pregnancy with gestational age 37-40-3/7 weeks. The main group consisted of 7 women with PE with a comparable gestational age (mean systolic blood pressure 157 ± 5 mm Hg, diastolic blood pressure 94 ± 2 mm Hg, and urinary protein excretion 2,12 ± 0,46 g/day). At the second stage, 12 patients with PE (aged 29 ± 1 year, gestation 37,9 ± 0,6 weeks, blood pressure 159 ± 5 / 99 ± 3 mm Hg) formed the main group. The control group included 11 healthy pregnant women comparable by gestational age. Venous blood samples were taken. Marinobufagenin level was determined by fluoroimmunoassay, spectrophotometry was used to assess the activity of erythrocyte Na/K-ATPase in the presence and absence of monoclonal antibody, DigiFab, magnesium sulfate. Results. The level of marinobufagenin in pregnant women with preeclampsia was almost 2,5-fold higher than in control group (1,056 vs. 0,421 nM). The activity of erythrocyte Na/K-ATPase in pregnant women with preeclampsia was 1,47 ± 0,1716 and 2,65 ± 0,16 mcmol Fn/mL/h (p < 0,01), respectively. When incubated with monoclonal antibodies erythrocyte Na/K-ATPase activity was 2,41 mcmol Fn/mL/h. When incubated with DigiFab there was a 3,5-fold increase in PE marinobufagenin plasma levels (1,38 ± 0,40 vs. 0,38 ± 0,10 nmol/L, p < 0,01) and a reduction of the erythrocyte Na/K-ATPase activity compared to control group (1,16 ± 0,11 vs. 2,80 ± 0,2 mkmol Fn/ml/h, p < 0,01). Ex vivo, 1 ug/ml DigiFab restores the activity of Na/K-ATPase (1,72 ± 0,13 mkmol Fn/ml/h, p < 0,01) and 3 mM magnesium sulfate amplifies DigiFab effect (2,3 ± 0,2 mkmol Fn/mL/h, p < 0,01).

Keywords: preeclampsia, cardiotonic steroids, marinobufagenin monoclonal antibody, DigiFab

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