Abstract 15777: Elabela, a Novel Apj-receptor Agonist, Improves Fluid Homeostasis and Reduces Cardio-renal Dysfunction During Acute Heart Failure (AHF)
Introduction: Hemodynamics alteration are the hallmark of cardiovascular (CV) and kidney dysfunction/injury induced by AHF. The apelinergic system regulates CV and renal function and is cardioprotective during experimental AHF. So far these effects are mainly held by Apelin-13 (APL-13) the most circulating fragment of the apelin family. ELABELA (ELA), a newly discovered endogenous ligand of the APJ-R, mainly expressed in kidney tissues, has recently described to modulate cardiac and renal functions. To date, the potential therapeutic impact of ELA supply during AHF with renal dysfunction is still unknown.
Hypothesis: Compare to APL-13 the cardio-renal effect and the therapeutic impact of ELA in healthy and septic rats with acute cardio-renal failure.
Methods: ELA impact of myocardial performance was assessed ex-vivo in Langendorff system. AHF and systemic inflammation was induced by cecal ligature and puncture (CLP) in rats. Peptides were infused I/V with fluid resuscitation in CLP rats or by osmotic pumps in healthy rats. Animals were maintained in metabolic cages to measure fluid balance (FB). Hemodynamics was assessed by echocardiography and LV catheterism with a pressure-volume probe. Heart, kidney and blood were collected for biological assays.
Results: In healthy rats, ELA stimulated heart and kidney functions to a similar level than APL-13. Perfused in CLP-rats, both APL-13 and ELA: i) limited mortality at 72h (survival: CLP: 0%, CLP+APL13: 40%, CLP+ELA: 40%, p<0.05) and ii) counteracted myocardial dysfunction with improved cardiac index (Sham: 20.1 mL/min/100g; CLP: 8.4 p<0.01 vs Sham; CLP+APL-13: 17.9 p<0.05 vs. CLP; CLP+ELA: 20.5 p<0.05) and LV pressure-volume relationship. Only ELA-treated CLP rats displayed i) a better LV filling with increased E-wave velocity and LV end-diastolic volume (Sham: 378; CLP: 264; CLP+APL-13: 333, CLP+ELA: 448 μL p<0.05), associated to a risen plasma volume and FB, ii) a reduction of kidney injury/dysfunction with improved creatinine clearance and reduced KIM-1 & micro-albuminuria. Moreover, ELA was more potent than APL-13 in reducing systemic and tissue inflammation.
Conclusions: ELABELA could be a potential new therapeutic drug to support hemodynamics and cardio-renal dysfunction during AHF.
Author Disclosures: D. Coquerel: None. X. Sainsily: None. F. Chagnon: None. A. Murza: None. L. Dumont: None. R. Dumaine: None. P. Sarret: None. E. Marsault: None. D. Salvail: None. M. Auger-Messier: None. O. lesur: None.
- © 2016 by American Heart Association, Inc.