title: β1-Adrenergic Inhibition Improves Cardiac and Vascular Function in Experimental Septic Shock.
abstract: OBJECTIVE
  Preliminary experimental data suggest that selective β1-blockers may improve ex vivo cardiac function in animal sepsis. Currently, the effects of esmolol on in vivo cardiac function and on vascular function are unknown. The present study was designed to examine the effects of the β1-selective blocker esmolol on myocardial and vascular function in peritonitis-induced septic rats and to explore the inflammatory pathways involved in this process.
  
  
  METHODS
  Randomized animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Wistar rats.
  
  
  METHODS
  Four hours after cecal ligation and puncture, Wistar rats were randomly allocated to the following groups: control, esmolol, norepinephrine (started at 18 hr after the surgery), and esmolol (started at 4 hr after the surgery) + norepinephrine (started at 18 hr after the surgery). Assessment at 18 hours after surgery was focused on cardiac contractility and vascular ex vivo function. Cardiac and vascular protein expressions of nuclear factor κB and endothelial nitric oxide synthase/Akt/inducible nitric oxide synthase pathways were assessed by Western blotting.
  
  
  RESULTS
  When compared with sham-operated animals, cecal ligation and puncture animals developed hypotension, cardiac depression, and vascular hyporesponsiveness to vasopressor treatment. Esmolol infusion increased cardiac contractility and restored mesenteric vasoreactivity. This effect was associated with a decrease in nuclear factor κB activation, an increase in Akt and endothelial nitric oxide synthase phosphorylation, and a decrease in inducible nitric oxide synthase expression both at the cardiac and vessel level. Esmolol infusion was also associated with an up-regulation in α1-vascular adrenoreceptors.
  
  
  CONCLUSIONS
  Adjunction of selective β1-blockade to standard septic shock management enhances intrinsic cardiac contractility and vascular responsiveness to catecholamines. These protective cardiovascular effects are likely predominantly attributed to the anti-inflammatory effect of esmolol.
authors.affiliation: 1CHU Nancy, Service de Réanimation Médicale Brabois, Pole Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France. 2INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France. 3Université de Lorraine, Nancy, France. 4INSERM U 1116, Groupe Choc, Equipe 1, Faculté de Médecine, Vandoeuvre les Nancy, France. 5Service Médecine Nucléaire et Nancyclotep, CHU Nancy-Brabois, Vandoeuvre les Nancy, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Kimmoun
authors.forename: Huguette
authors.initials: H
authors.lastname: Louis
authors.forename: Narimane
authors.initials: N
authors.lastname: Al Kattani
authors.forename: Julie
authors.initials: J
authors.lastname: Delemazure
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dessales
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wei
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Marie
authors.forename: Khodor
authors.initials: K
authors.lastname: Issa
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology*; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D018836:Inflammation Mediators; D016328:NF-kappa B; D011412:Propanolamines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D052250:Nitric Oxide Synthase Type III; C036604:esmolol; D009638:Norepinephrine