Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity.

Chen Wang,Hui-Bo Du,Zi-Gang Zhao,Chun-Yu Niu,Li-Min Zhang,Zhen-Ao Zhao,Jia-Yi Zhai

doi:10.3389/fphys.2021.728191

Chen Wang, Hui-Bo Du + Show 5 more

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https://doi.org/10.3389/fphys.2021.728191

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Abstract

Objective: The aim of this study was to clarify the role of autophagy in stellate ganglion block (SGB) reversing posthemorrhagic shock mesenteric lymph (PHSML)-mediated vascular hyporeactivity.Methods: Hemorrhagic shock model in conscious rats was employed to observe the effects of SGB (0.2 ml of 0.25% ropivacaine hydrochloride hydrate) and autophagy inhibitor 3-methyladenine (3-MA; 30 mg/kg) on the vascular reactivity of second-order rat mesenteric arteries in vitro, while the effects of PHSML (1 ml/kg) and autophagy agonist rapamycin (Rapa, 10 mg/kg) on the beneficial effect of SGB were investigated. The cellular viability, contractility, and autophagy-related protein expressions in vascular smooth muscle cells (VSMCs) were detected following treatments of PHSML, PHSML obtained from the rats that underwent hemorrhagic shock plus SGB (PHSML-SGB), and PHSML plus 3-MA (5 mM), respectively.Results: Hemorrhagic shock significantly decreased the vascular reactivity to gradient norepinephrine (NE), which is reversed by the SGB treatment and 3-MA administration. On the contrary, PHSML intravenous infusion and Rapa administration inhibited the vascular contractile responses in rats that underwent hemorrhagic shock plus SGB treatment. PHSML treatment significantly inhibited the cellular viability and contractility in VSMCs, increased the expressions of LC3-II and Beclin 1, and decreased the expression of p62, along with opposite appearances in these indices following PHSML-SGB treatment. In addition, 3-MA counteracted the adverse roles of PHSML in these indices in VSMCs.Conclusion: SGB inhibits PHSML-mediated vascular hyporeactivity by reducing the excessive autophagy in VSMCs.

Highlights

Hemorrhagic shock is a common and critical emergency in intensive care medicine, which is caused by acute massive bleeding following multiple traumas, peptic ulcers, obstetrical accidents, surgical accidents, and other factors (Cannon, 2018).Since bleeding could not be duly controlled and patients do not receive active and effective fluid resuscitation, the patients with massive hemorrhage will lead to shock and multiple organ injury characterized by high mortality
Hemorrhagic shock significantly decreased the vascular reactivity to gradient norepinephrine (NE), which is reversed by the stellate ganglion block (SGB) treatment and 3-MA administration
It would be better to seek a more direct method of observing the contractility of vascular smooth muscle cells (VSMCs) in future experiments. These results suggest that SGB improved the vascular reactivity of rats with hemorrhagic shock, which is related to the intestinal lymphatic pathway and its mechanism is related to the inhibition of excessive autophagy in VSMCs (Figure 6)

Summary

Introduction

Hemorrhagic shock is a common and critical emergency in intensive care medicine, which is caused by acute massive bleeding following multiple traumas, peptic ulcers, obstetrical accidents, surgical accidents, and other factors (Cannon, 2018).Since bleeding could not be duly controlled and patients do not receive active and effective fluid resuscitation, the patients with massive hemorrhage will lead to shock and multiple organ injury characterized by high mortality. Many studies demonstrated that posthemorrhagic shock mesenteric lymph (PHSML) return is a key link and basic pathway of hemorrhagic shock-induced uncontrolled inflammatory response and multiple organ injury (Deitch, 2012; Rocha-e-Silva, 2016; Nunns et al, 2018). Previous studies found that the blockage of PHSML by mesenteric lymphatic ligation or mesenteric lymph drainage improves the vascular reactivity in rats with hemorrhagic shock, and PHSML reduces the vascular reactivity to norepinephrine (NE) in vitro of vascular rings isolated from normal rats (Zhao et al, 2012). Since stellate ganglion (SG) is functionally the peripheral sympathetic ganglia, our previous studies found that stellate ganglion block (SGB) significantly prolongs the survival time and improves the intestinal barrier function in rats following hemorrhagic shock.

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