Role Of Ropivacaine-PLGA-nanoparticles Used In Upper Thoracic Epidural Space On Cerebral Vasospasm Following Subarachnoid Hemorrhage In The Rabbits

Objective:To investigate the effect of ropivacaine-nanoparticle used in upper thoracic epidural on cerebral vasospasm after subarachnoid hemorrhage in rabbits.Methods:Seventy-five healthy New Zealand rabbits with successful upper thoracic epidural catheter were selected,and divided randomly into 5 groups(n=15):shamoperated group(S),control group(C),placebo nanoparticles group(P),ropivacaine-loaded nanoparticles group(R), pump ropivacaine group(L).The animals in each group were divided into 3 subgroups randomly: 1 d, 7 d and 14 d group. SAH was developed by two injection of autoblood(0.5ml/kg) into the cistern magna. Neurobehavioral score was recorded after subarachnoid hemorrhage. Transcranial doppler ultrasonography(TCD) was used to detect the mean flow velocity(Vm) and peak systolic blood flow velocity(Vp) of basilar artery. The concentration of serum NSE and S100 B were measured with elisa method. The alteration of morphology and diameter of basilar artery was observed under light microscope. The expression of ET-1 and e NOS of basal artery endothelial cells was measured with immunohistochemistry method.Results: Compared with sham-operated group, it was higher in other groups about neurobehavioral scores, basilar arterial Vm and Vp, and serum NSE and S100B(P<0.05). The basal arterial diameter was more narrow, the basal arterial wall thicker, the structure disorder degree larger, the expression of ET-1 of basal artery endothelial cells higher, and the expression of e NOS significantly lower in other groups when compared with sham-operatied group(P<0.05). Compared with control group, the rabbits in R and L group obtained a significantly lower neurobehavioral score, Vm and Vp of basilar artery, and level of serum NSE and S100B(P<0.05). Besides, in R and L group, the arterial stenosis was milder, the arterial wall thickness lower and the structure disorder less obvious, the expression of ET-1 of basal artery endothelial cells significantly lower and expression of e NOS significantly higher(P<0.05). There was no significant statistical difference between R group and L group, and between P group and group C(P>0.05).Conclusion: In SAH rabbits, the application of ropivacaine-PLGA–nanoparticle in upper thoracic epidural space has benifical effects on CVS. It can not only improve cerebral blood flow, slow down the Vm and Vp of basilar artery and mitigate morphological changes of basilar artery, but also alleviate cerebral vasospasm. Furthermore, it can, to a certain extent, ameliorate secondary brain injury, decrease the level of serum NSE and the expression of S100 B, and then improve neurobehavioral function. Ropivacaine-PLGA–nanoparticle used in this way has a long term effect of blocking the cervical sympathetic nerve fibre which innervates cerebral vascular by releasing ropivacaine sustainedly. In this way, the durg might serve as a protective factor for the endothelial cells by up-regulating e NOS and down-regulating ET-1, which plays an important role in the protection of CVS after SAH.