Effect of Ropivacaine Hydrochloride Nanoliposomes on Delayed Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbits

Abstract

This research was aimed to investigate the effect of ropivacaine hydrochloride (RP-HCl) nanoliposome (NLP) on delayed cerebral vasospasm (DCVS) after subarachnoid hemorrhage (SAH) in rabbits. RP-HCl liposomes were prepared with RP-HCl, chloroform-ether, soybean phospholipid, dipalmitoyl phosphatidyl glycerol, and L-lysine 5% glucose solution by secondary emulsification, and blank NLP (without RP-HCl) was constructed at the same time. Additionally, an SAH model was also established by secondary blood injection into the large occipital pool. Forty New Zealand rabbits were randomly assigned into sham operation group (the injected liquid was 0.9% sodium chloride injection), control (Ctrl) group (the injected liquid was autologous blood and sodium chloride injection in sequence), no-load group (the injected liquid was autologous blood and blank liposomes in sequence), drug-loaded group (the injected liquid was autologous blood and RP-HCl NLP in sequence), and conventional group (the injected liquid was sodium chloride injection and ropivacaine in sequence), with eight rabbits in each group. The effects of RP-HCl NLP were analyzed through the changes in mean blood flow velocity (Vm), peak systolic blood flow velocity (Vp), neuron-specific enolase (NSE), S100B, diameter and apoptosis of the basilar artery (BA), vascular endothelial cell (EC) (VEC) endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). Results: the average particle size of RP-HCl NLP was 17.73±3.22 μm, and the average encapsulation efficiency was 86.40%. Relative to those before modeling, the Vm, Vp, NSE, and S100B levels in the BA of the five groups were increased on the 1st, 5th, and 10th days after modeling (P <0.05). In contrast to sham group, Vm, Vp, NSE, S100B, ET-1, and the apoptosis index were increased on the 1st, 5th, and 10th days after modeling in the other four groups, while the caliber and eNOS were decreased (P <0.05). The Vm, Vp, NSE, S100B, ET-1, and apoptosis index on the 1st, 5th, and 10th days after modeling in Ctrl and no-load groups were increased versus drug-loaded group, while the pipe diameter and eNOS were decreased (P <0.05). In conclusions, RP-HCl NLP can regulate the balance between ET-1 and eNOS, enhance neurological function, alleviate EC apoptosis, and reduce cerebral blood flow velocity to relieve DCVS after SAH.