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dc.contributor.authorSelli, Anders Lund
dc.contributor.authorKalasho, Adrina
dc.contributor.authorSmaglyukova, Natalia
dc.contributor.authorKondratiev, Timofei
dc.contributor.authorFuskevåg, Ole Martin
dc.contributor.authorSager, Georg
dc.contributor.authorDietrichs, Erik Sveberg
dc.date.accessioned2023-01-10T12:11:50Z
dc.date.available2023-01-10T12:11:50Z
dc.date.issued2022-12-15
dc.description.abstractBackground - Rewarming from hypothermia is associated with severe complications, one of which is hypothermia-induced cardiac dysfunction. This condition is characterized by decreased cardiac output accompanied by increased total peripheral resistance. This contributes to mortality rate approaching 40%. Despite this, no pharmacological interventions are recommended for these patients below 30 °C. Raising the intracellular levels of cAMP and/or cGMP, through PDE3- and PDE5-inhibitors respectively, have showed the ability to alleviate hypothermia-induced cardiac dysfunction in vivo. Drugs that raise levels of both cAMP and cGMP could therefore prove beneficial in patients suffering from hypothermia-induced cardiac dysfunction.<p> <p>Methods - The unselective PDE-inhibitor pentoxifylline was investigated to determine its ability to reach the intracellular space, inhibit PDE3 and PDE5 and inhibit cellular efflux of cAMP and cGMP at temperatures 37, 34, 30, 28, 24 and 20 °C. Recombinant human PDE-enzymes and human erythrocytes were used in the experiments. IC50-values were calculated at all temperatures to determine temperature-dependent changes.<p> <p>Results - At 20 °C, the IC50-value for PDE5-mediated enzymatic breakdown of cGMP was significantly increased compared to normothermia (IC50: 39.4 µM ± 10.9 µM vs. 7.70 µM ± 0.265 µM, p-value = 0.011). No other significant changes in IC50-values were observed during hypothermia.<p> <p>Conclusions - This study shows that pentoxifylline has minimal temperature-dependent pharmacodynamic changes, and that it can inhibit elimination of both cAMP and cGMP at low temperatures. This can potentially be effective treatment of hypothermia-induced cardiac dysfunction.en_US
dc.identifier.citationSelli AL, Kalasho A, Smaglyukova NN, Kondratiev T, Fuskevåg O, Sager gs, Dietrichs ES. Pharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermia. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2022;30(1)
dc.identifier.cristinIDFRIDAID 2094424
dc.identifier.doi10.1186/s13049-022-01060-y
dc.identifier.issn1757-7241
dc.identifier.urihttps://hdl.handle.net/10037/28119
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalScandinavian Journal of Trauma, Resuscitation and Emergency Medicine
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titlePharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermiaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)