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

Abstract

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.

β-Blockade use for Traumatic Injuries and Immunomodulation

“…(45) Chemical sympathectomy suppressed tissue type plasminogen activator, plasmin-antiplasmin complex, soluble thrombomodulin, and syndecan-1. (45) Reduction of sympathetic activation with chemical sympathectomy yielded antifibrinolytic and endothelial protective effects in rats with ATC.…”

“…(45) Chemical sympathectomy suppressed tissue type plasminogen activator, plasmin-antiplasmin complex, soluble thrombomodulin, and syndecan-1. (45) Reduction of sympathetic activation with chemical sympathectomy yielded antifibrinolytic and endothelial protective effects in rats with ATC. (45) Similarly, in a rodent laparotomy, hemorrhagic shock, and femur fracture model, rodents pre-treated with propranolol had decreased sympathetic tone, decreased fibrinolytic marker levels, and decreased tumor necrosis factor (TNF)-α and interleukin (IL)-6 without significant effects on fibrinogen or mortality.…”

Validation of acute traumatic coagulopathy in an ovine model of trauma and haemorrhage

“…In this study both markers were correlated with EXTEM A10, supporting the hypothesized contribution of glycocalyx degradation to coagulopathy. Rodent models of ATC suggest catecholamine excess may underlie glycocalyx degradation, with coagulopathy and glycocalyx shedding prevented by sympathetic blockade (241,242).However this model failed to demonstrate an association between glycocalyx degradation and catecholamine excess. Given the correlation between lactate, syndecan-1 and hyaluranon in this study it would appear that ischemia secondary to hypoperfusion is the more likely trigger for glycocalyx degradation in trauma.…”

“…Changes in the endothelial glycocalyx in trauma have predominately been attributed to this catecholamine surge, with sympathetic blockade effective in preventing coagulopathy and endothelial glycocalyx shedding in rodent models of haemorrhagic shock (241,242). However this finding was not supported in this thesis.…”

Macro-hemodynamic targets and hemostatic effects of fluid resuscitation during experimental hemorrhagic shock

“…Moreover, sympathetic denervation yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with TIC [68].…”