| Objective To investigate the effects of subarachnoid block on sedation of propofol inrats and probe into its possible mechanism by determine the concentration of lidocaine ofbrain, blood and spinal cord in rats.Methods With our institutional approval of animal research and use committee,Sprague-Dawley male rats were used in this study.40Sprague-Dawley rats were randomlyassigned to one of four groups and ten rats in each group: intrathecal lidocaine group,intravenous lidocaine group, intrathecal normal saline group and control group which wererespectively received lidocaine （2%,15μl） intrathecal injection, lidocaine （2%,15μl）intravenous injection and normal saline15μl intrathecal injection. And then infused propofoland the dosage of propofol required to ablate the eyelid reflex were recorded and comparedamong four groups. After propofol requirements measurement, the rats were sacrificed withan overdose of propofol in intrathecal lidocaine group for determination of brain and spinalcord lidocaine concentrations and intravenous lidocaine group for determination of brain andblood lidocaine concentrations and compared between two groups. A reversed phase highperformance liquid chromatographic （RP-HPLC） method was used for determination of brain,spinal cord, blood lidocaine concentrations in rats.Results The dose of propofol required to ablate the eyelid reflex were significantlydecreased in intrathecal lidocaine group （8.20±0.95） mg·kg-1compared with intravenouslidocaine group （10.61±0.92） mg·kg-1, intrathecal normal saline group （11.65±0.91） mg·kg-1and control group （11.26±1.23） mg·kg-1（P<0.01）. No significant difference was foundin the propofol requirement between the group of intrathecally administered normal saline,intravenously administered lidocaine and controls （P>0.05）. The brain lidocaineconcentration was not significantly difference between intrathecal lidocaine group（1.83±0.50） μg·g-1and intravenous lidocaine group（1.68±0.46） μg·g-1（P>0.05）. The concentrationof lidocaine in the spinal cord for the group given intrathecal lidocaine was significantlyhigher than in the brain（P﹤0.05）. The concentration of lidocaine in the brain for the groupgiven intravenously lidocaine was significantly higher than in the blood （P﹤0.05）.Conclusion The results showed that brain lidocaine concentration was notsignificantly difference between intrathecal lidocaine group and intravenous lidocaine group,however lidocaine subarachnoid block can reduce propofol requirement for sedation in rats.So its mechanism for sedation during subarachnoid block is not the indirect effect of localanesthetic to the brain by the spread of cerebrospinal fluid. Decreased stimulation of reticularactivating system followed by the interruption of the spinal afferent inputs would be areasonable mechanism. Objective To establish a reverse phase high performance liquid chromatographymethod to determine the concentration of lidocaine in brain and spinal cord of rats．Methods20rats were randomly divided into two groups. The rats in experimentalgroup were given in a volume of15μl intrathecally. The rats in control group wereeuthanized by injection of an overdose of pentobarbital. The lidocaine in brain and spinalcord of each rats was determined by ZORBAX Extend-C18Analytical （4.6mm×150mm,5μm） column with a mixture of methanol and water （0.3ml glacial acetic acid and0.6mltriethylamine was mixed in the100ml mixed liquor） according to62:38. PH was adjusted to4.9by glacial acetic acid. The elution rate was0.8ml·min-1, the detection wavelength was210nm, and the column temperature was30℃．Results The linear range for lidocaine in spinal cord of rats was from0.365μg·ml-1to14.6μg·ml-1with a good correlation coefficient. The linear coefficient relation wasY=29.521X+15.729（r=0.9957）. The extraction recoveries of high, middle and lowconcentrations were97.09%,103.38%, and94.02%, respectively. The average recovery was（98.17±6.21）%. The coefficient variations of intra-and inter-day of lidocaine for0.73μg·ml-1,3.65μg·ml-1,10.95μg·ml-1were less than7.45%and11.75%. The linear range forlidocaine in brain of rats was from0.365μg·ml-1to14.6μg·ml-1with a good correlationcoefficient. The linear coefficient relation was Y=37.591X+11.255（r=0.9997）. The extractionrecoveries of high, middle and low concentrations were98.94%,103.89%and101.01%,respectively. The average recovery was（101.28±6.72）%. The coefficient variations of intra- and inter-day of lidocaine for0.73μg·ml-1,3.65μg·ml-1,10.95μg·ml-1were less than7.35%and9.86%.Conclusion The method is simple, accurate and useful．It could be applied to monitorthe concentration of lidocaine in brain and spinal cord of rats, and could be used to thepharmaceutical research when the lidocaine was applied to the intraspinal anesthesia．... |
PDF Full Text Request