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12 February 2015 : Animal Research

Impact of β-Adrenoceptor Blockade on Systemic Inflammation and Coagulation Disturbances in Rats with Acute Traumatic Coagulopathy

Lin XuABCDEF, Wen-kui YuABCDEF, Zhi-liang LinBC, Shan-jun TanBC, Xiao-wu BaiBC, Kai DingBC, Ning LiAG

DOI: 10.12659/MSM.893544

Med Sci Monit 2015; 21:468-476

Abstract

BACKGROUND: Sympathetic hyperactivity occurs early in acute traumatic coagulopathy (ATC) and is closely related to its development. β-adrenoceptor antagonists are known to alleviate adverse sympathetic effects and improve outcome in various diseases. We investigated whether β-blockers have protective effects against inflammation and endothelial and hemostatic disorders in ATC.

MATERIAL AND METHODS: ATC was induced in male Sprague-Dawley rats by trauma and hemorrhagic shock. Rats were randomly assigned to the sham, ATCC (ATC control), and ATCB (ATC with beta-adrenoceptor blockade) groups. Rats were injected intraperitoneally with propranolol or vehicle at baseline. Heart rate variability (HRV) and markers of inflammation, coagulation, and endothelial activation were measured, and Western blotting analysis of nuclear factor (NF)-κB was done after shock. Separate ATCC and ATCB groups were observed to compare overall mortality.

RESULTS: HRV showed enhanced sympathetic tone in the ATCC group, which was reversed by propranolol. Propranolol attenuated the induction of pro-inflammatory cytokines TNF-α and IL-6, as well as fibrinolysis markers plasmin antiplasmin complex and tissue-type plasminogen activator. The increased serum syndecan-1 and soluble thrombomodulin were inhibited by propranolol, and the NF-κB expression was also decreased by propranolol pretreatment. But propranolol did not alter overall mortality in rats with ATC after shock.

CONCLUSIONS: Beta-adrenoceptor blockade can alleviate sympathetic hyperactivity and exert anti-inflammatory, anti-fibrinolysis, and endothelial protective effects, confirming its pivotal role in the pathogenesis of ATC. Its mechanism in ATC should be explored further.

Keywords: Adrenergic beta-Antagonists - pharmacology, Analysis of Variance, Animals, Blood Coagulation Disorders - etiology, Blotting, Western, Cytokines - metabolism, Heart Rate - drug effects, Kaplan-Meier Estimate, NF-kappa B - metabolism, Propranolol - pharmacology, Rats, Rats, Sprague-Dawley, Systemic Inflammatory Response Syndrome - drug therapy, Wounds and Injuries - complications

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750