The Research Of Lipid Emulsion Rescue Central Nervous System Toxicity Of Local Anesthetic In Rats

Objective:To observe effects of lipid emulsion intravenous injection on central nervous system toxicity of lidocaine hydrochloride, levobupivacaine hydrochloride or ropivacaine hydrochloride which were perfused into lateral ventricle separately in SD rats and explore the mechanism of lipid emulsion rescue central nervous system toxicity of local anesthetic in rats.Methods:100 adult SD rats(male or female), weight 240-300g, randomly divided into four groups:A (sham group), B (lidocaine hydrochloride group), C(ropivacaine hydrochloride group), D(levobupivacaine hydrochloride group),and B, C, D groups are divided into three subgroups(toxic group, postconditioning group; preonditioning group, n=10). Rats were anaesthetized by intraperitoneal injection of 2% Sodium pentobarbital(40mg·kg-1), spontaneous breathing remained, and then tail vein puncture, tracheal intubation and femoral artery puncture were performed with continuous injection of ringer's solution by computerized infusion pump at the rate 1ml·kg-1·min-1. At the same time, monitor ECG?HR?RR?MAP of rats and record the data.After ventricle puncture, local anesthetics were injected by microsyringe slowly (the dosage of 0.75% lidocaine hydrochloride 2?l·kg-1,0.75% levobupivacaine hydrochloride 1.4?l·kg-1 and 1% ropivacaine hydrochloride 2?l·kg-1 into lateral ventricle at the speed of 50?l·min-1). Postconditioning by lipid emulsion group:when the rat respiratory arrest, injected lipid emulsion into tail vein 5ml·kg-1 and computerized infusion pump at the rate 0.25ml·kg-1·min-1. Preconditioning by lipid emulsion group:injected lipid emulsion into tail vein 5ml·kg-1 and computerized infusion pump at the rate 0.25ml·kg-1·min-1 for 30min after LA injected into lateral ventricle. Sham group:Inject same dose 0.9%NS into lateral ventricle. Record the injected dosage, the time of respiratory arrest and arrhythmia in groups.Estimate the animal neurobehavioral scores before test and 6h,12h,24h after operation. The rats were sacrificed and the brains were collected 24h after operation, then examine the brain by Hematoxylin-eosin staining.Results:1.Animal models Lateral ventricle was punctured successfully in all rats. Toxic reaction happened after the lateral ventricle injection of LA in all rats. Rats in toxic groups died from breathing arrest after the lateral ventricle injection of LA; five rats in other groups died for cardiopulmonary arrest during operation, then five rats were added. Finally,100 rats were studied in experimental statistics.2.The time of respiratory arrest, heart rates, blood pressure simultaneously after injection of drugs. Respiratory arrest was not detected in all preconditioning groups.(1)After intracerebroventricular injection of LA, the time of respiratory arrest:among toxic groups, there had no significant difference between group B and group C (p>0.05), but there had significant difference when both of them compared with group D(p<0.01). Among postconditioning groups, there had no significant difference between group B and group C (p>0.05), but there had significant difference when both of them compared with group D(p<0.01). Within group B, group C and group D, there had no significant difference of the time between toxic group and postconditioning group (p>0.05). All rats had no respiratory arrest in postconditioning group in group B, C and D.(2)The recovery time (from respiratory arrest):in LE postconditioning groups, there had significant difference between group B, C and D (p<0.01), the order of recovery time as follows:lidocaine group> bupivacaine group> ropivacaine group.(3)Heart rates at respiratory arrest in toxic groups and postconditioning groups after intracerebroventricular injection of LA:in toxic groups, there had no significant difference between group B and group D (p>0.05), but there had significant difference when both of them compared with group C(p<0.01). Within group B, group C and group D, there had no significant difference of heart rate between toxic group and postconditioning group (p>0.05).(4)Blood pressure at respiratory arrest in toxic groups and postconditioning groups after intracerebroventricular injection of LA: in toxic groups, there had no significant difference between group B and group D (p>0.05), but there had significant difference when both of them compared with group C(p<0.01). Within group B, group C and group D, there had no significant difference of heart rate between toxic group and postconditioning group (p>0.05).3. Arrhythmia and its onset time:Arrhythmia was detected only in toxic groups in group B, group C and group D. The Arrhythmia included bradycardia, premature contraction, irregular heart beats. There had significant difference between group B, C and D (p<0.01), the order of onset time as follows:lidocaine group> bupivacaine group> ropivacaine group.4. Neruological behavior scores Before the operation, neruological behavior scores were normal in all rats. The rats in all toxic group of B, C, D group all died. In postconditioning group and preconditioning group,the scores of B, C, D group were significantly lower than sham group at all time points after operation (p<0.01), but no significant difference between B, C, D groups (p>0.05); Within postconditioning group and preconditioning group, there had no significant difference in B, C, D group at all time points after operation (p>0.05).5. Neuronal density Neuronal density in hippocampal CA1 was normal in every group, had no significant difference (p>0.05).Conclusion:1. LE postconditioning could rescue CNS toxicity caused by injecting LA into lateral ventricle.2. LE preconditioning could prevent CNS toxicity by injecting LA into lateral ventricle.