ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock
| Autor: | Jérôme Côté, Robert Dumaine, Philippe Sarret, David Coquerel, Alexandre Murza, Xavier Sainsily, Mannix Auger-Messier, Frederic Chagnon, Lauralyne Dumont, Dany Salvail, Eric Marsault, Olivier Lesur |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Inotrope Male medicine.medical_specialty Vasopressin Peptide Hormones Hemodynamics 030204 cardiovascular system & hematology Critical Care and Intensive Care Medicine Real-Time Polymerase Chain Reaction Sepsis 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Kidney Septic shock business.industry medicine.disease Shock Septic Apelin Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Echocardiography Shock (circulatory) Cardiology Cytokines Intercellular Signaling Peptides and Proteins medicine.symptom business Biomarkers |
| Zdroj: | Critical care medicine. 45(11) |
| ISSN: | 1530-0293 |
| Popis: | Objectives Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown. Design, setting, and subjects Interventional study in a rat model of septic shock (128 adult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function. Experiments were performed in a tertiary care University-based research institute. Interventions Polymicrobial sepsis-induced cardiac dysfunction was produced by cecal ligation puncture to assess hemodynamic efficacy, cardioprotection, and biomechanics under acute or continuous infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 µg/kg/hr, respectively) versus normal saline. Measurements and main results Apelinergic agonists improved 72-hour survival after sepsis induction, with ELA providing the best clinical outcome after 24 hours. Apelinergic agonist infusion counteracted cecal ligation puncture-induced myocardial dysfunction by improving left ventricular pressure-volume relationship. ELA-treated cecal ligation puncture rats were the only group to 1) display a significant improvement in left ventricular filling as shown by increased E-wave velocity and left ventricular end-diastolic volume, 2) exhibit a higher plasma volume, and 3) limit kidney injury and free-water clearance. These beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a distinctive regulation of pituitary vasopressin release. Conclusions Activation of the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and survival after cecal ligation puncture-induced sepsis. However, ELA proved better than Apelin-13 by improving fluid homeostasis, cardiovascular hemodynamics recovery, and limiting kidney dysfunction in a vasopressinergic-dependent manner. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|