Abstract | RATIONALE: OBJECTIVES: METHODS: MEASUREMENTS: Hepatocellular metabolism and liver blood flow were measured by plasma disappearance rate of indocyanine green (PDR(ICG)) as a sensitive marker of liver function. MAIN 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.
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Authors | Alexander Raddatz, Darius Kubulus, Johannes Winning, Inge Bauer, Sascha Pradarutti, Beate Wolf, Sascha Kreuer, Hauke Rensing |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 174
Issue 2
Pg. 198-207
(Jul 15 2006)
ISSN: 1073-449X [Print] United States |
PMID | 16627864
(Publication Type: Journal Article)
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Chemical References |
- Adrenergic beta-Agonists
- Propanolamines
- Dobutamine
- Heme Oxygenase-1
- esmolol
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Topics |
- Adrenergic beta-Agonists
(pharmacology)
- Animals
- Aorta
(metabolism)
- Blood Gas Analysis
- Dobutamine
(pharmacology)
- Dose-Response Relationship, Drug
- Heme Oxygenase-1
(blood)
- Hemodynamics
(drug effects)
- Jejunum
(metabolism)
- Kidney
(metabolism)
- Liver
(blood supply, drug effects, physiopathology)
- Liver Diseases
(etiology, physiopathology, prevention & control)
- Male
- Propanolamines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(etiology, physiopathology, prevention & control)
- Shock, Hemorrhagic
(blood, physiopathology)
- Up-Regulation
(physiology)
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