01-11-2011 | Experimental
Beta-1 blocker improves survival of septic rats through preservation of gut barrier function
Published in: Intensive Care Medicine | Issue 11/2011
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Objective
Since recent study demonstrated beneficial effects of β-adrenergic blocker in sepsis, we tested the hypothesis that infusion of selective β1-blocker, esmolol, improves outcome in sepsis by modulating inflammatory responses and gut barrier function.
Design
Prospective randomized animal study.
Setting
University research laboratory.
Subjects
Male Wistar rats.
Interventions
To assess the effects of esmolol infusion on survival time, 19 animals that underwent cecal ligation and perforation were randomized into control (n = 9) or esmolol (n = 10) groups, the latter of which received esmolol infusion (15 mg/kg/h) throughout the study period. In an additional 20 animals, levels of tumor necrosis factor-α (TNF-α) in both plasma and intraperitoneal fluid were measured, and mesenteric lymph nodes (MLNs) and ileum were excised for evaluation of bacterial translocation and mucosal injury at the 18-h study period.
Measurements and results
Mean survival time in the esmolol group was significantly longer compared with the control group (69.5 ± 26.8 versus 28.6 ± 11.0 h). Plasma TNF-α was not detectable in either group, while intraperitoneal fluid TNF-α level was elevated in the control group but significantly depressed in the esmolol group (16.8 ± 10.7 versus 5.4 ± 7.1 pg/ml, P < 0.05). Simultaneously, the Escherichia coli positive rate of MLNs was higher (100% versus 44%, P < 0.05) and the gut mucosal injury score was elevated (4.1 ± 0.6 versus 2.8 ± 0.6, P < 0.01) in the control compared with the esmolol group.
Conclusions
Beta-1 blocker therapy improves outcome in sepsis possibly through modulation of gut mucosal integrity and local inflammatory response.