0100. Apelin is cardioprotective and life-saving over dobutamine in a murine model of endotoxin-induced myocardial dysfunction
© Lesur et al; licensee Springer. 2014
Published: 26 September 2014
only 35-45% of septic patients do respond to DOB, and
numerous side-effects of DOB can be observed, including potential harmful impact on cardiomyocyte function. Apelin (APLN) is a powerful inotrope, is widely expressed by the cardiovascular system with its receptor APJ-R, and should be considered as an alternative noncatecholaminergic support.
Perform a comparative evaluation of APLN-13 (APLN active peptide) vs DOB in terms of hemodynamic efficacy, cardioprotection and outcome in a model of “sepsis-induced cardiac dysfunction”.
A rat model of LPS-induced myocardial dysfunction (E. Coli 055:B5, 10-12mg/kg intraperitoneal).
APLN-13 vs DOB (0.23 vs 7.5µg/kg/min i.v continuous infusion respectively, as determined by preliminary experiments with or without “in parallel” fluid resuscitation (saline, 2mL/kg/hr).
in vivo: echocardiography, final hemodynamics; urine output, weight and plasma volume variation, survival study, ex vivo: Langendorff dP/dt, in vitro: APJ-R and beta1-adrenergic receptor (AR) myocardial expressions, Pi3K/Akt/GSK3/mTOR activation-expression profiles, cTnI (troponin, myocardial injury) and cleaved caspase-3 (apoptosis).
APLN further dampened down LPS-induced overphosphorylation/inhibition of Pi3K/Akt/mTOR/GSK3 and reduced injury/apoptosis (i.e. cTNI and cleaved caspase-3 expressions).
APLN potentially offers distinctive mechanisms of hemodynamics, cardioprotective effects, and survival benefits, over DOB. Chemical optimization of APLN-13 with more extensive preclinical data, would pave the way for first phase clinical trials.
Canadian Heart & Stroke Foundation.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.