Wilson J, Higgins D, Hutting H, Serkova N, Baird C, Khailova L, Queensland K, Weitzel L, Tran ZV, Wischmeyer PE.; Crit Care. 2013 Sep 10;17(5):R195. [Epub ahead of print]
Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized other injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade, however outcome data in experimental models has 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 q 8 hours x 24 hours) 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.
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