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http://dx.doi.org/10.25673/115167
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DC Element | Wert | Sprache |
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dc.contributor.author | Rayo-Abella, Lina M. | - |
dc.contributor.author | Grundig, Peter | - |
dc.contributor.author | Bernhardt, Max N. | - |
dc.contributor.author | Hofmann, Britt | - |
dc.contributor.author | Neumann, Joachim | - |
dc.contributor.author | Gergs, Ulrich | - |
dc.date.accessioned | 2024-03-05T07:36:05Z | - |
dc.date.available | 2024-03-05T07:36:05Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/117123 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/115167 | - |
dc.description.abstract | OR-1896 ((R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide) is the main active metabolite of levosimendan. However, nobody has reported a positive inotropic effect of OR-1896 in isolated human cardiac preparations. The mechanism of action of OR-1896 remains controversial. Hence, we wanted to know whether OR-1896 exerts a positive inotropic effect in humans and what might be the underlying mechanism. Therefore, we measured the contractile effects of OR-1896 (0.01–10 µM cumulatively applied) in isolated electrically stimulated (1 Hz) human right atrial preparations (HAP) obtained during cardiac surgery. OR-1896, given alone, exerted time- and concentration-dependent positive inotropic effects; 1-µM OR-1896 increased force by 72 ± 14.7% (p < 0.05, n = 6) and shortened the time of relaxation by 10.6 ± 3.6% (p < 0.05, n = 11) in HAP started at 0.1 µM, plateaued at 1-µM OR-1896, and was antagonized by 1-µM propranolol. The maximum positive inotropic effect of OR-1896 in human right atrial preparations was less than that of 10-µM isoprenaline. EMD 57033 (10 µM), a calcium sensitizer, enhanced the force of contraction further in the additional presence of 1-µM OR-1896 by 109 ± 19% (p < 0.05, n = 4). Cilostamide (10 µM), an inhibitor of phosphodiesterase III given before OR-1896 (1 µM), blocked the positive inotropic effect of OR-1896 in HAP. Our data suggest that OR-1896 is, indeed, a positive inotropic agent in the human heart. OR-1896 acts as a PDE III inhibitor. OR-1896 is unlikely to act as a calcium sensitizer in the human heart. | eng |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.ddc | 610 | - |
dc.title | OR-1896 increases force of contraction in the isolated human atrium | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | Naunyn-Schmiedeberg's archives of pharmacology | - |
local.bibliographicCitation.volume | 396 | - |
local.bibliographicCitation.issue | 12 | - |
local.bibliographicCitation.pagestart | 3823 | - |
local.bibliographicCitation.pageend | 3833 | - |
local.bibliographicCitation.publishername | Springer | - |
local.bibliographicCitation.publisherplace | Berlin | - |
local.bibliographicCitation.doi | 10.1007/s00210-023-02592-5 | - |
local.subject.keywords | OR1896, mouse atrium, human atrium, phospholamban | - |
local.openaccess | true | - |
dc.identifier.ppn | 1853810398 | - |
cbs.publication.displayform | 2023 | - |
local.bibliographicCitation.year | 2023 | - |
cbs.sru.importDate | 2024-03-05T07:35:40Z | - |
local.bibliographicCitation | Enthalten in Naunyn-Schmiedeberg's archives of pharmacology - Berlin : Springer, 1873 | - |
local.accessrights.dnb | free | - |
Enthalten in den Sammlungen: | Open Access Publikationen der MLU |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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s00210-023-02592-5.pdf | 1.72 MB | Adobe PDF | ![]() Öffnen/Anzeigen |