• Frederic Chagnon, David Coquerel, Dany Salvail, Eric Marsault, Robert Dumaine, Mannix Auger-Messier, Philippe Sarret, and Olivier Lesur.
• 1Soins Intensifs Médicaux et Service de Cardiologie, Université de Sherbrooke, Sherbrooke, QC, Canada.2Centre de Recherche du CHUS (CR-CHUS), Sherbrooke, QC, Canada.3IPS Therapeutique Inc., Sherbrooke, QC, Canada4Département de Pharmacologie-Physiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.5Institut de Pharmacologie de Sherbrooke (IPS), Université de Sherbrooke, Sherbrooke, QC, Canada.6Département de Médecine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
• Crit. Care Med. 2017 Apr 1; 45 (4): e391-e398.

ObjectiveDobutamine is the currently recommended β-adrenergic inotropic drug for supporting sepsis-induced myocardial dysfunction when cardiac output index remains low after preload correction. Better and safer therapies are nonetheless mandatory because responsiveness to dobutamine is limited with numerous side effects. Apelin-13 is a powerful inotropic candidate that could be considered as an alternative noncatecholaminergic support in the setting of inflammatory cardiovascular dysfunction.DesignInterventional controlled experimental animal study.SettingTertiary care university-based research institute.SubjectsOne hundred ninety-eight adult male rats.InterventionsUsing a rat model of "systemic inflammation-induced cardiac dysfunction" induced by intraperitoneal lipopolysaccharide injection (10 mg/kg), hemodynamic efficacy, cardioprotection, and biomechanics were assessed under IV osmotic pump infusions of apelin-13 (0.25 μg/kg/min) or dobutamine (7.5 μg/kg/min).Measurements And Main ResultsIn this model and in both in vivo and ex vivo studies, apelin-13 compared with dobutamine provoked distinctive effects on cardiac function: 1) optimized cardiac energy-dependent workload with improved cardiac index and lower vascular resistance, 2) upgraded hearts' apelinergic responsiveness, and 3) consecutive downstream advantages, including increased urine output, enhanced plasma volume, reduced weight loss, and substantially improved overall outcomes. In vitro studies confirmed that these apelin-13-driven processes encompassed a significant and rapid reduction in systemic cytokine release with dampening of myocardial inflammation, injury, and apoptosis and resolution of associated molecular pathways.ConclusionsIn this inflammatory cardiovascular dysfunction, apelin-13 infusion delivers distinct and optimized hemodynamic support (including positive fluid balance), along with cardioprotective effects, modulation of circulatory inflammation and extended survival.

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