title: Apelin Compared With Dobutamine Exerts Cardioprotection and Extends Survival in a Rat Model of Endotoxin-Induced Myocardial Dysfunction.
abstract: OBJECTIVE
  Dobutamine 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.
  
  
  METHODS
  Interventional controlled experimental animal study.
  
  
  METHODS
  Tertiary care university-based research institute.
  
  
  METHODS
  One hundred ninety-eight adult male rats.
  
  
  METHODS
  Using 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).
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  In 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.
authors: 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.
authors: Frederic
authors: F
authors: Chagnon
authors: David
authors: D
authors: Coquerel
authors: Dany
authors: D
authors: Salvail
authors: Eric
authors: E
authors: Marsault
authors: Robert
authors: R
authors: Dumaine
authors: Mannix
authors: M
authors: Auger-Messier
authors: Philippe
authors: P
authors: Sarret
authors: Olivier
authors: O
authors: Lesur
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D015996:Survival Rate; D014655:Vascular Resistance / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C495199:apelin-13 peptide; D004280:Dobutamine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases