Impact of ß-adrenoceptor blockade on systemic inflammation and coagulation disturbances in rats with acute traumatic coagulopathy.

BACKGROUND: Sympathetic hyperactivity occurs early in acute traumatic coagulopathy (ATC) and is closely related to its development. ß-adrenoceptor antagonists are known to alleviate adverse sympathetic effects and improve outcome in various diseases. We investigated whether ß-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.

Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic-vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. Male Sprague-Dawley rats were randomly assigned to sham, ATC control (ATCC) and ATC with sympathectomy by 6-hydroxydopamine (ATCS) group. Sham animals underwent the same procedure without trauma and bleeding. Following trauma and hemorrhage, rats underwent heart rate variability (HRV) test, which predicts autonomic dysfunction through the analysis of variation in individual R-R intervals. Then, rats were euthanized at baseline, and at 0, 1 and 2 h after shock and blood gas, conventional coagulation test and markers of inflammation, coagulation, fibrinolysis, endothelial damage and catecholamine were measured. HRV showed an attenuation of total power and high frequency, along with a rise of low frequency and low frequency : high frequency ratio in the ATC rats, which both were reversed by sympathectomy in the ATCS group. Additionally, sympathetic denervation significantly suppressed the increase of proinflammatory cytokines, tumor necrosis factor-α and the fibrinolysis markers including tissue-type plasminogen activator and plasmin-antiplasmin complex. Serum catecholamine, soluble thrombomodulin and syndecan-1 were also effectively inhibited by sympathectomy. These data indicated that autonomic dysfunction in ATC involves both sympathetic activation and parasympathetic inhibition. Moreover, sympathectomy yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with ATC. The role of autonomic neuropathy in ATC should be explored further.

Protective effects of terminal ileostomy against bacterial translocation in a rat model of intestinal ischemia/reperfusion injury.

AIM: To investigate the effects of terminal ileostomy on bacterial translocation (BT) and systemic inflammation after intestinal ischemia/reperfusion (I/R) injury in rats. METHODS: Thirty-two rats were assigned to either the sham-operated group, I/R group, I/R + resection and anastomosis group, or the I/R + ileostomy group. The superior mesenteric artery was occluded for 60 min. After 4 h, tissue samples were collected for analysis. BT was assessed by bacteriologic cultures, intestinal permeability and serum levels of endotoxin; systemic inflammation was assessed by serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10, as well as by the activity of myeloperoxidase (MPO) and by intestinal histopathology. RESULTS: Intestinal I/R injury not only caused morphologic damage to ileal mucosa, but also induced BT, increased MPO activity and promoted the release of TNF-α, IL-6, and IL-10 in serum. BT and ileal mucosa injuries were significantly improved and levels of TNF-α and IL-6 in serum were decreased in the I/R + ileostomy group compared with the I/R + resection and anastomosis group. CONCLUSION: Terminal ileostomy can prevent the detrimental effects of intestinal I/R injury on BT, intestinal tissue, and inflammation.