1.Effect of neurotoxicity of ropivacaine, bupivacaine and lidocaine on central nervous system of mice
Xiaogao JIN ; Ailin LUO ; Jintao WANG
Chinese Journal of Tissue Engineering Research 2005;9(45):145-147
BACKGROUND: It is demonstrated that ropivacaine has less toxicity than bupivacaine, but bupivacaine has higher liposolubility and efficacy, so a less dose of bupivacaine is needed in clinical comparing with ropivacaine. Serious convulsion is usually followed by cardiotoxicity induced by local anesthetics. The ratio of medial lethal dose (CD50) and median convulsant doses (LD50) is usually used to assess the comparative safety of local anesthetics.OBJECTIVE: To establish CD50 and LD50 of 2% lidocaine, 0.75% bupivacaine and 0.75% ropivacaine for Kunming mice and select proper indicator for neurotoxicity, then to compare neurotoxicity of the three local anesthetics on central nervous system.DESIGN: Randomized and controlled study.SETTING: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: This study was carried out from July to December in 2002 in the Laboratory of Anesthesiology, Tongji Hospital, Tonji Medical College, Huazhong University of Science and Technology. Totally 310Kunming mice aged of 1-month with clean grade were enrolled in this study.METHODS: ① To determine the relation of dose of local anesthetics with conclusion rate and death rate in mice. Todetermine the dose-effect relationship for ropivacaine, 50 mice were selected and divided into 5 groups with 10rates in each group who received dose of 76.80, 68.69, 61.44,49.15, 31.46 mg/kg respectively. For bupivacaine, 90 mice were divided into 9 groups, with 10 rates in each group who received intraperitoneal dose of 50.00, 47.29, 44.72, 42.29, 40.00, 35.78, 32.00, 28.62, 25.60 mg/kg respectively. For lidocaine, 100 mice were divided into 10 groups,with10rates in each group who received dose of 183.11, 163.77, 146.48,131.02, 117.19, 93.75, 75.00, 60.00, 48.00, 38.40 mg/kg respectively. For each local anes thetic, the rates of convulsion or death were tried to distribute on both sides of 50% symmetrically. On the dose-response curve, 4or 5 well-spaced points were obtained for probit analysis to determine CD50 and LD50 of each agent. ② The effect of different dose of lidocaine on conclusion duration and c-fos expression in brain with different doses.Forty mice were divided into 4 groups with 10 rates in each group who received 0, 30%, 60% and 90% convulsant doses of lidocaine intraperitoneally. The duration of convulsion were recorded carefully for the convulsant mice that should be marked correctly for next procedure. Two hours later, the convulsant mice were anesthetized deeply and fixed by transcardiac perfusion for Immunohistochemistry to detect c-Fos expression. ③ Comparison of neurotoxicity induced by CD50 of three agents.Thirty mice were randomly divided into 3 groups with 10 rates in each group who received intraperitoneally CD50 of lidocaine, bupivacaine and ropivacaine respectively. The duration of convulsion and the number of neurons expressed with c-Fos in mice brain were compared among these three groups.MAIN OUTCOME MEASURES: The response of mice to intraperitoneal local anesthestics, duration of convusion and c-Fos expression using immunohistochemistry methods.RESULTS: Date of totally 310 mice was entered into final results analysis. ① The relation of dose of local anesthetics and conclusion rate or death rate in mice. The therapeutic index (LD50/CD50) of 2% lidocaine,0.75% bupivacaine and 0.75% ropivacaine were 2.89, 1.48 and 1.34, respectively. ② c-Fos expression induced by lidocaine in mice brain: The cFos expression in mice brain was mainly distributed in three zones-thalamencephal, hypothalamus, amydyla and pyriform cortex. ③ Compare of the duration of convulsion and number of neurons with c-Fos expression induced by different dose oflidocaine. Compared with control group, the duration of convulsion and number of neurons with c-Fos expression in amydyla and pyriform cortex all increased significantly in CD30, CD60and CD90 group (P < 0.05). ④ Neurotoxicity induced by CD50 of lidoacaine, bupivacaine and ropivacasine The duration of convulsion and expression of c-fos in amydyla and pyriform cortex were significantly increased in ropivacaine group compared to bupivacaine or lidocaine group intraperitoneally (P < 0.05). There were no significant differences in the duration of convulsion and expression of c-Fos between lidocaine and bupivacaine group (P > 0.05).CONCLUSION: Compared with bupivacaine, ropivacaine produced less toxicity when identical dose was used in clinic. It is indicated that if an accidental convulsion induced by ropivacaine, it may be more severe than that induced by correspondent either lidocaine or bupivacaine. It may be the reason that ropivacaine have less lipid solubility, absorbed easily from this tissue compartment, and to get a high concentration in blood.
2.Isoflurane enhances the expression of cytochrome C by facilitation of NMDA receptor in developing rat hippocampal neurons in vitro.
Yilin, ZHAO ; Xiaogao, JIN ; Jintao, WANG ; Lei, TAN ; Shiyong, LI ; Ailin, LUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(6):779-83
This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (I(NMDA)) and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25, 0.5, 0.75, 1 minimum alveolar concentration (MAC))]. The peak of I(NMDA) was recorded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane (0.25, 0.5, 0.75 and 1 MAC) potentiated the amplitude of I(NMDA) by (116±8.8)%, (122±11.7)%, (135±14.3)% and (132±14.6)%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P<0.05). It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor.
3.Application of CT venography in diagnosis and treatment of Budd-Chiari syndrome
Xiaogao WANG ; Shiyuan CHEN ; Biao SHI ; Xiaochun QIAO ; Yong GAO ; Chaowen YU ; Zhonglin NIE
Chongqing Medicine 2016;45(8):1043-1045
Objective To investigate the application value of CT venography(CTV) in the diagnosis and treatment of Budd‐Chiari syndrome(BCS) .Methods 58 patients with BBCS in our hospital from January 2012 to January 2014 were performed the CTV examination .The inferior vena cava ,hepatic vein ,portal vein and collateral vessels were performed the reconstruction analysis . Results All the patients were definitely diagnosed as BCS after completing CTV examination ,including :19 cases of inferior vena cava(IVC) diaphragm type ,15 cases of short IVC segment occlusion ,8 cases of long IVC segment occlusion ,9 cases of hepatic vein stenosis or occlusion ,7 cases complicated by fresh thrombosis .In addition ,the different degrees of compensatory expansion of col‐lateral vesse ,intuition and comprehensiveness ,can display the position ,character and length of lesion vessel ,also observes the de‐grees of collateral vessels expansion and liver cirrhosis .
4.Effects of isoflurane anenthesia on myocyte enhancer factor 2 signaling pathway in neonatal rat hippocampus
Yilin ZHAO ; Ailin LUO ; Xiaogao JIN ; Jintao WANG ; Lei TAN ; Qingyu SHI ; Shiyong LI
Chinese Journal of Anesthesiology 2011;31(6):714-716
Objective To investigate the effects of isoflurane anenthesia on myocyte enhancer factor 2(MEF2) signaling pathway in neonatal rat hippocampus. Methods Twenty-four 5-day-old SD rats of both sexes,weighing 10-13 g, were randomly divided into 2 groups ( n = 12 each): control group (group C) and isoflurane group (group I). In group I, 1.5% isoflurane in 100% O2 was inhaled for 6 h. Group C received no treatment.Three rata in each group were sacrificed at 2, 4, 6 h of isoflurane anenthesia and 24 h after isoflurane anenthesia (T1-4), and the hippocampi removed for determination of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsinⅠ mRNA expression (by PT-PCR) and synapsin Ⅰ protein expression (by Western blot).Results Compared with group C, the expression of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsin Ⅰ mRNA at T1-3 and synapsin Ⅰ protein at T2-4 was up-regulated in group I ( P < 0.05). Conclusion Inhalation of anaesthetic concentration of isoflurane may affect synapse formation during the development of central nervous system by actirating hippocampal MEF2 signaling pathways in neonatal rats.
5.Isoflurane Enhances the Expression of Cytochrome C by Facilitation of NMDA Receptor in Developing Rat Hippocampal Neurons In Vitro
ZHAO YILIN ; JIN XIAOGAO ; WANG JINTAO ; TAN LEI ; LI SHIYONG ; LUO AILIN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(6):779-783
This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (INMDA) and the expression of cytochrome C in cultured developing rat hippocampal neurons.The hippocampi were dissected from newborn Sprague-Dawley rats.Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25,0.5,0.75,1 minimum alveolar concentration (MAC))].The peak of INMDA was recorded by means of the whole cell patch clamp technique.The cytochrome C level was detected by Western blotting and quantitative real-time PCR.Our results showed that isoflurane (0.25,0.5,0.75 and 1 MAC) potentiated the amplitude of INMDA by (116±8.8)%,(122±11.7)%,(135±14.3)% and (132±14.6)%,respectively,and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner.The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P<0.05).It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons,which may be mediated by facilitation of NMDA receptor.
6.Implementation and Evaluation of Subject Diagnosis and Treatment Module Based on Drug Clinical Trial Mana- gement System
Xiaoyun WANG ; Xin SHAO ; Yang YANG ; Zhiming GUO ; Ziyin ZHANG ; Chen XI ; Xiaogao ZHANG ; Junying LIAN ; Xiaojian ZHANG ; Jianbo GAO ; Yuhong LI
China Pharmacy 2021;32(13):1537-1542
OBJECTIVE:To provide reference for the c onstruction of subject diagnosis and treatment scheme in drug clinical trials. METHODS :The subject diagnosis and treatment module was developed and implemented in our hospital on the basis of CTMS,and its effects were evaluated. RESULTS :A subject diagnosis and treatment module was established in CTMS of our hospital. Within one year from the launch of the module in the middle of October ,2019,the overall number of subjects in the group showed an increasing trend ,and the overall mean dropout rate of subjects was 0.16%. The data interface of CTMS system , hospital information system (HIS),laboratory information management system ,medical imaging information system had been established,so as to realize the synchronization of subject information (displaying subject identification in HIS system )and the interaction of diagnosis and treatment information and billing data (patients and subjects were charged separately ). Since the launch of the module ,the amount of data generated by the interface had been increasing ,and the number of departments producing the subject diagnosis and treatment business had been increasing month by month. Compared with subject diagnosis and treatment project based on HIS system ,the number of subject diagnosis and treatment business based on CTMS system was increased significantly(P<0.05). CONCLUSIONS :The subject diagnosis and treatment module based on CTMS improves the efficiency of subject diagnosis and treatment project implementation and financial settlement ,and realizes the efficient implementation of drug clinical trial projects in large general hospitals.