Digitalis

Haustein, Knut-Olaf

doi:10.1016/0163-7258(82)90026-2

Cited by 19 publications

(12 citation statements)

References 482 publications

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“…On the basis of the increase in force of contraction, DPI was developed as a cardiotonic. Cardiotonics can induce or aggravate arrhythmias as is known for Na'/ K+ ATPase inhibiting digitalis glycosides (Haustein, 1982) and for adenosine 3': 5'-cyclic monophosphate (cyclic AMP) elevating drugs (Opie & Lubbe, 1979;Kanayama et al, 1982;Podzuweit et al, 1985). The mechanism of the positive inotropic effect of DPI is prolongation of the open state of sodium channels (Buggisch et al, 1985) and a sensitization of contractile proteins to Ca2" (Herzig & Quast, 1984) without involvement of cyclic AMP .…”

Section: Introductionmentioning

confidence: 99%

Antiarrhythmic effects of DPI 201‐106

Scholtysik¹,

Williams²

1986

British J Pharmacology

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Section: Introductionmentioning

confidence: 99%

Antiarrhythmic effects of DPI 201‐106

Scholtysik¹,

Williams²

1986

British J Pharmacology

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“…The binding of ouabain to the ␣ -subunit of Na,K-ATPase leads to an imbalance of its ionic transport, leading to accumulation of intracellular Na + and a consequent increase in intracellular Ca 2+ through the Na + /Ca 2+ exchanger. This effect is the basis of its therapeutic use in the treatment of cardiac dysfunction as it increases the contraction strength of the cardiac muscle [2] .…”

mentioning

confidence: 99%

mCD14 Expression in Human Monocytes Is Downregulated by Ouabain via Transactivation of Epithelial Growth Factor Receptor and Activation of p38 Mitogen-Activated Protein Kinase

Valente¹,

Nascimento

Araújo

et al. 2009

Neuroimmunomodulation

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Background and Aims: The steroid ouabain is found in plasma and in many mammalian tissues, and is now considered as a hormone. In the immune system, ouabain regulates a number of lymphocyte functions, but little is known about its effects on monocyte function. Monocytes are important for adequate immune responses. The aim of this work was to analyze the effect of ouabain on mCD14 expression, a surface molecule involved in the response against Gram-negative bacteria and phagocytosis. Methods: Human peripheral blood mononuclear cells obtained from healthy donors were separated by density gradient centrifugation. Monocytes were separated by adherence and treated for 24 h with 100 nM ouabain. mCD14, CD1a and P-p38 expression was analyzed by flow cytometry. Inhibitors of cell-signaling pathways, i.e. SB202190, reduced glutathione, rottlerin, tyrphostin A23, genistein, chelerythrine chloride, PD98059, PP1 and Ly 294002, were used concomitantly with ouabain to observe their effect on mCD14 expression. Results: Ouabain induced a significant decrease in mCD14 expression. This feature was not related to receptor endocytosis or cell death. Furthermore, mCD14 downregulation did not reflect a shift in differentiation into dendritic cells because this hormone failed to induce CD1a expression. Amongst several inhibitors of cell-signaling pathways triggered by ouabain, only epidermal growth factor receptor (EGFR) and p38 mitogen-activated protein kinase (MAPK) inhibitors (tyrphostin A23 and SB202109) significantly reverted the effect of ouabain on mCD14 expression. Accordingly, the levels of P-p38 were increased on monocytes after ouabain treatment. However, incubation with epidermal growth factor did not alter mCD14 expression. Conclusion: These findings suggest that ouabain downregulates mCD14 expression on monocytes through EGFR transactivation and p38 MAPK activation.

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“…Digitalis-induced electrolyte imbalance might be the third mechanism, since the inhibition of the Na+, K+-ATPase system by ouabain has been well known. It occurs in all excitable tissues and structures associated with active Na', K' transport (Haustein, 1983), and aggravation of digitalis-induced A-V block, resulting from additional His-Purkinje block rather than from further depression of intranodal conduction, has been reported in conditions of high K' levels (Watanabe and Dreifus, 1970). Lastly, it is speculated that the prolongation of the HV interval and QRS duration was a specific change observed only in rats.…”

Section: Discussionmentioning

confidence: 99%

“…Some m n s were pmposed for this unexpected result. One of them is that direct effects of ouabain on the conduction system itself result in electmphysiological changes consistent with the development of anhythmias (Haustein, 1983;Hoffman, 1969). The rat has been known to be one of the "digitalis-lesssensitive" species compared to cats, dogs, and guinea pigs (Gunn, 1908).…”

Section: Discussionmentioning

confidence: 99%

The applicability of noninvasive his bundle electrogram to assessing the effect of digitalis on atrioventricular conduction

Otsuka

Nojima

Saito

et al. 1986

Clinical Cardiology

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Summary:His bundle electrograms were recorded by a signal averaging technique using the Takayasu vectorial lead system, and effects of ouabain on the atrioventricular conduction were investigated using Wistar rats. Ouabain was given intraperitoneally at 30 min intervals in doses of 1-40 mg/kg. When ouabain dosage was increased to 20 mg/kg, the prolongation of PQ interval became prominent and P waves were hidden on the preceding T waves. Dose-related prolongation of PQ and AH intervals was observed in the 1-15 mg/kg dosages. Ouabaininduced ventricular arrhythmias occurred in the 30 mg/kg dosage. Dose-related prolongation of QRS duration and HV interval was observed in the 1-25 mg/kg dosages. These prolongations were significant by the analysis of variance (p

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Digitalis

Cited by 19 publications

References 482 publications

Antiarrhythmic effects of DPI 201‐106

Antiarrhythmic effects of DPI 201‐106

mCD14 Expression in Human Monocytes Is Downregulated by Ouabain via Transactivation of Epithelial Growth Factor Receptor and Activation of p38 Mitogen-Activated Protein Kinase

The applicability of noninvasive his bundle electrogram to assessing the effect of digitalis on atrioventricular conduction

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