apelin-13-peptide and Shock--Septic

Apelins are potential candidate therapeutic molecules for hemodynamic support. The objective of this study was to assess the hemodynamic impacts of apelin-13 in a neonatal lamb model of septic shock.. Lambs were randomized to receive apelin-13 or normal saline. Septic shock was induced by injecting a fecal slurry into the peritoneal cavity. Lambs underwent volume repletion (30 mL/kg over 1 h) followed by intravenous administration of 5 incremental doses (D) of apelin-13 (D1 = 0.039 to D5 = 19.5 µg/kg/h) or normal saline.. Following fecal injection, mean arterial pressure (MAP) and cardiac index (CI) dropped in both groups (p < 0.05). The MAP decreased non-significantly from D1 to D5 (p = 0.12) in the saline group, while increasing significantly (p = 0.02) in the apelin group (-12 (-17; 12) vs. +15 (6; 23) % (p = 0.012)). Systemic vascular resistances were higher in the apelin-13 group at D5 compared to the saline group (4337 (3239, 5144) vs. 2532 (2286, 3966) mmHg/min/mL, respectively, p = 0.046). The CI increased non-significantly in the apelin-13 group.. Apelin-13 increased MAP in a neonatal lamb septic shock model.. Administration of apelin-13 stabilized hemodynamics during the progression of the sepsis induced in this neonatal lamb model. Systemic vascular resistances were higher in the apelin-13 group than in the placebo group. This suggests ontogenic differences in vascular response to apelin-13 and warrants further investigation. This study suggests that apelin-13 could eventually become a candidate for the treatment of neonatal septic shock.

Topics: Animals; Hemodynamics; Peritonitis; Saline Solution; Sheep; Shock, Septic

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.. 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.. 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.. 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.. 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.

Topics: Animals; Biomarkers; Cytokines; Disease Models, Animal; Echocardiography; Hemodynamics; Intercellular Signaling Peptides and Proteins; Male; Peptide Hormones; Rats; Real-Time Polymerase Chain Reaction; Shock, Septic