title: Dobutamine improves liver function after hemorrhagic shock through induction of heme oxygenase-1.
abstract: BACKGROUND
  Induction of heme oxygenase-1 (HO-1) protects the liver against reperfusion injury after hemorrhagic shock. Previous data suggest that the beta(1)-adrenoceptor agonist dobutamine induces HO-1 in hepatocytes.
  
  
  OBJECTIVE
  To investigate the functional significance of dobutamine pretreatment for liver function after hemorrhagic shock in vivo.
  
  
  METHODS
  Anesthetized rats received either Ringer's (Vehicle/Shock), 10 microg/kg/min of the beta(1)-adrenoceptor agonist dobutamine (Dob/Shock), or 10 microg/kg/min dobutamine and 500 microg/kg/min of the beta(1)-adrenoceptor antagonist esmolol (Dob/Esmolol/Shock) for 6 h. Hemorrhagic shock was induced thereafter (mean arterial pressure, 35 mm Hg for 90 min). Animals were resuscitated with shed blood and Ringer's. In addition, the HO pathway was blocked after dobutamine pretreatment with 10 micromol/kg tin-mesoporphyrin-IX (Dob/SnMP/Shock) or animals received 100 mg/kg of the carbon monoxide donor dichloromethane (DCM/Shock).
  
  
  METHODS
  Hepatocellular metabolism and liver blood flow were measured by plasma disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver function.
  
  
  RESULTS
  Pretreatment with dobutamine induced HO-1 in pericentral hepatocytes and improved PDR(ICG) (Vehicle/Shock: 11.7 +/- 8.12%/min vs. Dob/Shock: 19.7 +/- 2.46%/min, p = 0.006). Blockade of the HO pathway after preconditioning and the combined pretreatment with dobutamine and esmolol decreased PDR(ICG) (Dob/SnMP/Shock: 12.6 +/- 4.24%/min, p = 0.011; Dob/Esmolol/Shock: 10.2 +/- 4.34%/min, p = 0.008). Pretreatment with a carbon monoxide donor improved PDR(ICG) (DCM/Shock: 18 +/- 3.19%/min, p = 0.022) compared with Vehicle/Shock.
  
  
  CONCLUSIONS
  These results suggest a beta(1)-adrenoceptor-dependent hepatic up-regulation of HO-1 and a better maintained hepatocellular function after hemorrhagic shock in animals pretreated with dobutamine. The improved hepatocellular function may be in part mediated by carbon monoxide because of up-regulation of HO-1. Pretreatment with dobutamine might be a potential means of pharmacologic preconditioning before ischemia-reperfusion of the liver.
authors.affiliation: Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, D-66421 Homburg/Saar, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Raddatz
authors.forename: Darius
authors.initials: D
authors.lastname: Kubulus
authors.forename: Johannes
authors.initials: J
authors.lastname: Winning
authors.forename: Inge
authors.initials: I
authors.lastname: Bauer
authors.forename: Sascha
authors.initials: S
authors.lastname: Pradarutti
authors.forename: Beate
authors.initials: B
authors.lastname: Wolf
authors.forename: Sascha
authors.initials: S
authors.lastname: Kreuer
authors.forename: Hauke
authors.initials: H
authors.lastname: Rensing
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001784:Blood Gas Analysis; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D004280:Dobutamine; D051547:Heme Oxygenase-1; C036604:esmolol