Role And Mechanism Of Stellate Ganglion Block Improving The Function Of Myocardial Contraction Following Hemorrhagic Shock

Background: Hemorrhagic shock is a common clinical critical disease;the reduction of myocardial contractility and heart pump function are important factor in the process of shock deterioration.Post hemorrhagic shock mesenteric lymph(PHSML)is a key factor in myocardial injury and dysfunction following hemorrhagic shock.Stellate ganglion block(SGB)has been widely used in clinical practice through reducing sympathetic excitability and reducing inflammatory response,but it is remain unclear whether it has a similar therapeutic effect on severe shock and whether there has a relation with PHSML-mediated myocardial injury? Cell autophagy is an important form of cell injury,whether autophagy is associated with myocardium injury following hemorrhagic shock,and whether autophagy involves in the SGB reducing the myocardial injury are need further investigated.Objective: In this study,we observed the effect of SGB and autophagy inhibitors on myocardial structure,cell autophagy and the function of isolated cardiac contraction following hemorrhagic shock with awake model of hemorrhagic shock in rats.Furthermore,we investigated the effects of PHSML and autophagy agonists on SGB,to determine the roles of autophagy and PHSML in SGB reducing myocardial injury and dysfunction following hemorrhagic shock,and to provide experimental evidence for the prevention and treatment of myocardial contractile dysfunction following severe shock.Methods: Healthy adult SPF male Wistar rats were randomly divided into eight groups: Sham,Sham+SGB,Shock,Shock+SGB,Shock +SGB+ PHSML,Shock+SGB+Rapamycin(RAPA),Shock+ 3-methyladenine(3-MA),Shock+SGB+PHSML+3-MA.According to the experimental design,implemented different measures,at 60 min after low blood pressure,3 h after the resuscitation or the corresponding time point,clipped the heart quickly.Then detected the relevant indicators of cardiac systolic function left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),heart rate(HR),maximal increase of left ventricular pressure and decrease rate(±dp/dtmax)by using isolated heart perfusion system.The myocardium tissue was made by routine method to observe the histological changes of myocardium.Observed the expression of special marker of myocardium tissue autophagy microtubule-associated protein light chain 3(LC3-?)by immunohistochemical staining.Results:(1)Myocardial tissue morphological change: Myocardial fibers arranged neatly,the structure was clear,the cells without edema,no abnormalities in mesenchyme in the Sham and Sham+SGB groups;the myocardial structure of the Shock group showed significant injury,manifested fracture,arranged disorder in the myocardial fiber,mesenchyme edema.Compared with the Shock group,the the degree of disorder myocardial fibers in the Shock+SGB was mild and no abnormalities in mesenchyme.Compared with the Shock+SGB group,intravenous transfusion of PHSML aggravated myocardial injury,performance in the fiber breakage,degree of disorder increased,visible necrosis,mesenchyme edema and widening,visible inflammatory cell infiltration;Compared with the Shock+SGB group,the myocardial fibers were no significantly abnormalities in the Shock+SGB+RAPA group.The treatment of 3-MA significantly decreased the degree of myocardial tissue injury in the Shock and Shock+SGB+PHSML groups,showed mild myocardial fiber breakage,disordered arrangement,mesenchyme no obvious abnormalities.(2)The expression of cardiomyocyte LC3-?: LC3-? expressed in the cytoplasm of cardiomyocytes;the expression of LC3-? had no obvious change in the Sham+SGB and Sham groups.The expression of LC3-? in Shock group was stronger than that in the Sham group;The treatment of SGB and 3-MA reduced the expression of LC3-?;Intravenous administration of PHSML inhibited SGB reducing the expression of LC3-?;The treatment of 3-MA reduced the negative effect of PHSML;There was no significant difference in the expression of LC3-? between Shock+SGB+RAPA and Shock+SGB groups.(3)Change of systolic function in isolated heart: SGB increased the HR and +dP/dtmax levels in Sham group;the indexes of ±dP/dtmax and LVSP decresed in shock group;The treatment of SGB and 3-MA increased ±dP/dtmax and LVSP of isolated heart in Shock group respectively;Intravenous transfusion PHSML abolished the beneficial effect of SGB on isolated cardiac function in Shock group,which is further reversed by the treatment of 3-MA;RAPA had no obvious effect on isolated cardiac function with the treatment of the Shock+SGB group.Conclusion: SGB reduced the degree of myocardial injury following hemorrhagic shock and improved the systolic function of isolated heart.Its mechanism is related to the reduction of cell autophagy and PHSML backflow.The related mechanism need further investigate.