title: Effects of low doses of esmolol on cardiac and vascular function in experimental septic shock.
abstract: Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock.
  
  
  
  Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg-1.h-1), CLP + E-5 (esmolol: 5 mg.kg-1.h-1), CLP + E-18 (esmolol: 18 mg.kg-1.h-1). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting.
  
  
  
  CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hypo-responsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18.
  
  
  
  In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.
authors.affiliation: INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France.|Université de Lorraine, Nancy, France.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wei
authors.affiliation: Université de Lorraine, Nancy, France.|INSERM U 1116, Groupe Choc, Equipe 1, Faculté de Médecine, Vandoeuvre les Nancy, France.
authors.forename: Huguette
authors.initials: H
authors.lastname: Louis
authors.affiliation: INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Université de Lorraine, Nancy, France.|Unité ESPRI-BioBase, CHRU Nancy, Vandoeuvre les Nancy, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Albuisson
authors.affiliation: INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France.|Université de Lorraine, Nancy, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Orlowski
authors.affiliation: INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France. b.levy@chru-nancy.fr.|Université de Lorraine, Nancy, France. b.levy@chru-nancy.fr.|CHU Nancy, Service de Réanimation Médicale Brabois, Pole Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France. b.levy@chru-nancy.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
authors.affiliation: INSERM U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Service de Réanimation Médicale Brabois, Pole Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Kimmoun
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D011412:Propanolamines; C036604:esmolol
keywords: Esmolol; Heart function; Inflammation; Sepsis; Vasoreactivity