Effects of Fab digoxin-specific antibody(Fab) on mean arterial pressure (MAP) in severe preeclampsia(PE)

Adair, D

doi:10.1016/s0895-7061(97)88679-7

Cited by 15 publications

(8 citation statements)

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“…Likewise, antiouabain antibody ex vivo did not alter activity of NKA in preeclampsia erythrocytes. In previous reports, in preeclampsia, Digibind exhibited antihypertensive effects at doses ranging from 0.1 to 1.5 mg/kg [3,23,24]. In the present work, a lower concentration of Digibind (1 μg/ml in vitro ), which is comparable to clinically effective concentrations of this drug, did not significantly alter the activity of NKA in the erythrocytes from patients with preeclampsia.…”

Section: Discussionsupporting

confidence: 58%

“…In 16 Dahl-S rats rendered hypertensive by a 4-week administration of 8% NaCl diet, we compared effects of anti-MBG 3E9 mAb ( n =8) and Digibind (0.5 mg/kg) following single intraperitoneal administration. Dose of 3E9 mAb was determined as described above (Dahl-S on a high NaCl diet), and dose of Digibind was comparable to that effectively administered to patients with preeclampsia in previous reports (0.1–1.5 mg/kg) [3,22,23]. Following administration of antibodies, SBP was measured in 3 h after the treatment and every 12 h thereafter for 48 h. Animals were placed in the metabolic chambers and 24-h urine samples were collected for determination of urinary sodium excretion.…”

Section: Methodsmentioning

confidence: 99%

“…Anti-MBG or antiouabain antibodies were used at concentrations that, in vitro , reversed the MBG-induced 75% inhibition of rat kidney NKA (α-1 isoform) or ouabain-induced 75% inhibition of NKA from rat fetal brain (α-3 isoform), respectively [11]. Digibind (GlaxoSmithKline) was used at concentrations 1 and 10 μg/ml, which are in the same range as doses of Digibind previously used to treat patients with preeclampsia [3,22,23]. …”

Section: Methodsmentioning

confidence: 99%

“…Later, Adair et al [22] reported another case of successful use of Digibind in preeclampsia. Subsequently, the same group, in a placebo-controlled double-blinded study [23], demonstrated that Digibind lowered the blood pressure in 13 patients with postpartum preeclampsia. Importantly, Digibind did not exert adverse effects in these studies.…”

Section: Introductionmentioning

confidence: 99%

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Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension

Федорова¹,

Kolodkin

et al. 2008

Journal of Hypertension

158

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Background Levels of marinobufagenin (MBG), an endogenous bufadienolide Na/K-ATPase (NKA) inhibitor, increase in preeclampsia and in NaCl-sensitive hypertension. Methods We tested a 3E9 monoclonal anti-MBG antibody (mAb) for the ability to lower blood pressure (BP) in NaCl-sensitive hypertension and to reverse the preeclampsia-induced inhibition of erythrocyte NKA. Measurements of MBG were performed via immunoassay based on 4G4 anti-MBG mAb. Results In hypertensive Dahl-S rats, an intraperitoneal administration of 50 μg/kg 3E9 mAb lowered BP by 40 mmHg and activated Na/K-pump in thoracic aorta by 51%. NaCl supplementation of pregnant rats (n = 16) produced a 37 mmHg increase in BP, a 3.5-fold rise in MBG excretion, and a 25% inhibition of the Na/K-pump in the thoracic aorta, compared with pregnant rats on a normal NaCl intake. In eight pregnant hypertensive rats, 3E9 mAb reduced the BP (25 mmHg) and restored the vascular Na/K-pump. In 14 patients with preeclampsia (mean BP, 126 ± 3 mmHg; 26.9 ± 1.4 years; gestational age, 37 ± 0.8 weeks), plasma MBG was increased three-fold and erythrocyte NKA was inhibited compared with that of 12 normotensive pregnant women (mean BP, 71 W 3 mmHg)(1.5 ± 0.1 vs. 3.1 ± 0.2 μmol Pi/ml/h, respectively; P < .01). Ex-vivo 3E9 mAb restored NKA activity in erythrocytes from patients with preeclampsia. As compared with 3E9 mAb, Digibind, an affinity-purified antidigoxin antibody, was less active with respect to lowering BP in both hypertensive models and to restoration of NKA from erythrocytes from patients with preeclampsia. Conclusion Anti-MBG mAbs may be a useful tool in the studies of MBG in vitro and in vivo and may offer treatment of preeclampsia.

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Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension

Федорова¹,

Kolodkin

et al. 2008

Journal of Hypertension

158

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“…Previous published work has shown that in vitro treatment of erythrocytes from preeclamptic patients with Digibind could restore the cell Na + /K + -ATPase activity 3. Furthermore, administration of Digibind to both antepartum and postpartum women with preeclampsia could improve maternal symptoms and increase fetoplacental perfusion10,11 (Dr Adair’s unpublished data), which suggest that Digibind could be a potential therapy for preeclampsia. To study if Digibind exerts beneficial effects on endothelial cells, we examined the role of Digibind in TNFα-induced inflammatory response in endothelial cells.…”

Section: Introductionmentioning

confidence: 95%

Digibind attenuates cytokine TNFα-induced endothelial inflammatory response: potential benefit role of Digibind in preeclampsia

et al. 2009

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Objective: Exaggerated inflammatory response occurs in preeclampsia. Preeclampsia is also associated with elevated endogenous digoxin-like factors (EDLFs). Clinical data suggest that Digibind (a polyclonal sheep digoxin binding Fab fragment) binds to EDLF and may have the potential to attenuate vasoconstriction and other clinical symptoms of preeclampsia. This study was undertaken to determine if Digibind could attenuate increased endothelial inflammatory response induced by tumor necrosis factor-a (TNFa).Study Design: Confluent endothelial cells were treated with TNFa at different concentrations with or without Digibind in culture. Endothelial adhesion molecule ICAM, VCAM and E-selectin expressions were determined by an immunoassay directly detected on the endothelial surface. Effects of Digibind on TNFa-induced extracellular signalregulated kinase and Na þ /K þ -ATPase expressions were also examined.Result: (1) TNFa induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFa-induced upregulation of endothelial E-selectin, ICAM and VCAM expressions. The blocking effect was in a concentration dependent manner; (3) Digibind had no effects on TNFa-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFa-induced downregulation of Na þ /K þ -ATPase b1 expression.Conclusion: Digibind may exert beneficial effects by preserving cell membrane Na þ /K þ -ATPase function and consequently to offset increased inflammatory response in endothelial cells.

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Animal Models

Venuto¹,

Lindheimer²

2009

Chesley's Hypertensive Disorders in Pregnancy

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Effects of Fab digoxin-specific antibody(Fab) on mean arterial pressure (MAP) in severe preeclampsia(PE)

Cited by 15 publications

References 0 publications

Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension

Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension

Digibind attenuates cytokine TNFα-induced endothelial inflammatory response: potential benefit role of Digibind in preeclampsia

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