医学
体外膜肺氧合
断奶
心脏病学
内科学
充氧
体外
重症监护医学
作者
Christian Alcaraz Frederiksen,Roni Nielsen,Anne Sofie Frederiksen,Steffen Christensen,Jacob Greisen,Henrik Vase,Brian Bridal Løgstrup,Søren Mellemkjær,Henrik Wiggers,H. Mølgaard,C J Terkelsen,Steen Hvitfeldt Poulsen,Hans Eiskjær
标识
DOI:10.1093/eurheartj/ehy566.p5689
摘要
1200 Acute heart failure-treatment harvested to evaluate O-GlcNAc impact on calcium actors.In parallel, LPS and CLP studies were completed with a Kaplan-Meier mortality or an adapted SOFA score evaluations, respectively.Results: In both models, NButGT efficiently increased cardiac O-GlcNAc (+300% vs Ctrl) with no modification of its three regulatory enzymes (GFAT, OGT and OGA; vs LPS-FR or CLP).NButGT induced an amelioration of the outcome with (i) a 57.2% decrease in lactatemia (vs LPS-FR) (ii) a 3-fold increase in survival time (vs LPS-FR) and (iii) a 23% decrease in SOFA score (vs CLP).Moreover, organs function was significantly improved; among them heart (heart rate -5.5% vs LPS-FR; -10% vs CLP), kidney (creatinine -56.5% vs LPS-FR; -27% vs CLP) and it also had a beneficial impact on mean AP (MAP +10% vs CLP).These beneficial effects were associated with a restoration of SERCA2a protein level (-56% vs LPS-FR, ns vs Ctrl) without modification of its regulator (phospholamban) or ryanodine receptor. Conclusion:Our results demonstrate that an acute O-GlcNAc stimulation is a potential new therapeutic target in septic shock.In our two models, we especially showed an improvement of cardiac function potentially through an improvement of cardiomyocytes' calcium handling.We are currently validating our approach at different doses and ages to be able to transfer our results to the clinic.
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