Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.

Wilson, Joel

Higgins, David

Hutting, Haley

Serkova, Natalie

Baird, Christine

Khailova, Ludmila

Queensland, Kelly

Vu Tran, Zung

Weitzel, Lindsay

Wischmeyer, Paul E

England

2016-11-06T18:25:42Z

2013-09-10

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.

http://www.ncbi.nlm.nih.gov/pubmed/24020447

cc12889

1466-609X

https://hdl.handle.net/10161/12991

eng

Springer Science and Business Media LLC

Crit Care

10.1186/cc12889

Adrenergic beta-Antagonists

Animals

Drug Administration Schedule

Enzyme Induction

Heme Oxygenase (Decyclizing)

Lung

Male

Metabolic Diseases

Propranolol

Rats

Rats, Sprague-Dawley

Sepsis

Survival Rate

Treatment Outcome

Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.

Journal article

http://www.ncbi.nlm.nih.gov/pubmed/24020447

R195

5

Anesthesiology

Anesthesiology, Critical Care Medicine

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

School of Medicine

Published online

17