Beta-1 blocker improves survival of septic rats through preservation of gut barrier function.

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.