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Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.
Abstract
INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been
associated with improved outcome in burn injury. It has been hypothesized that injuries
leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade;
however, outcome data in experimental models have been contradictory. Thus, we investigated
the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat
shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal
ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving
either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively)
of propranolol or control (normal saline), underwent CLP and were monitored for survival.
Additionally, lung and blood samples were collected at 6 and 24 hours for analysis.
Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven
days following CLP, propranolol improved survival versus control (P < 0.01). Heart
rates in the propranolol-treated rats were approximately 23% lower than control rats
(P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different
between groups. Metabolic analysis of lung tissue demonstrated an increase in lung
ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids
to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory
cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression
of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally,
propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key
cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression
was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease
mortality during sepsis potentially via a combination of improving metabolism, suppressing
aspects of the inflammatory response and enhancing tissue protection.
Type
Journal articleSubject
Adrenergic beta-AntagonistsAnimals
Drug Administration Schedule
Enzyme Induction
Heme Oxygenase (Decyclizing)
Lung
Male
Metabolic Diseases
Propranolol
Rats
Rats, Sprague-Dawley
Sepsis
Survival Rate
Treatment Outcome
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https://hdl.handle.net/10161/12991Published Version (Please cite this version)
10.1186/cc12889Publication Info
Wilson, Joel; Higgins, David; Hutting, Haley; Serkova, Natalie; Baird, Christine;
Khailova, Ludmila; ... Wischmeyer, Paul E (2013). Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction,
and improves survival following experimental sepsis. Crit Care, 17(5). pp. R195. 10.1186/cc12889. Retrieved from https://hdl.handle.net/10161/12991.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Paul Edmund Wischmeyer
Professor of Anesthesiology
Paul Wischmeyer M.D., EDIC, FASPEN, FCCM is a critical care, perioperative, and nutrition
physician-researcher who specializes in enhancing preparation and recovery from surgery,
critical care and COVID-19. He serves as a Tenured Professor of Anesthesiology and
Surgery at Duke. He also serves as the Associate Vice Chair for Clinical Research
in the Dept. of Anesthesiology and Director of the TPN/Nutrition Team at Duke. Dr.
Wischmeyer earned his medical degree with honors at T

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