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

Objective: Since recent study demonstrated beneficial effects of beta-adrenergic blocker in sepsis, we tested the hypothesis that infusion of selective beta 1-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-alpha (TNF-alpha) 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-alpha was not detectable in either group, while intraperitoneal fluid TNF-alpha 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.