Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a cont...Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a continuous Rb administration method based on effect-site concentrations calculated by a pharmacokinetic/pharmacodynamics model during propofol, sevoflurane, and desflurane anesthesia. Methods: The 36 enrolled patients were equally divided into three groups (P;propofol, S;sevoflurane, and D;desflurane groups). After induction and administration of Rb 0.6 mg/kg, we calculated the simulated effect-site concentration at the point which the first twitch (%T1) recovered to > 0% and defined this as the Rb recovery concentration (Rbr.c.) level appropriate for continuous rocuronium administration. The continuous administration doses of Rb were adjusted to maintain Rbr.c. during surgery. The Rbr.c. and the recovery time at %T1 > 25% were recorded for each type of anesthesia. Results: Rbr.c. (μg/mL) for the P, S, and D groups were 1.54 ± 0.2, 1.24 ± 0.2, and 1.09 ± 0.2, respectively. Continuous administration doses (μg/kg/min) in the P, S, and D group were 6.7 ± 0.9, 5.2 ± 1.0, and 4.5 ± 0.8, respectively. Rbr.c. and continuous doses in the S and D groups were lower than the P group. Neuromuscular relaxations during surgery in the S and D groups were more strongly maintained than for the P group. There was also a significantly prolonged recovery duration for the %T1 > 25% in the D versus the other two groups (P < 0.05). Conclusion: Results showed that our continuous administration method was effective for maintaining sufficient muscle relaxation without excessively prolonged recovery effects for both sevoflurane and desflurane as well as propofol anesthesia.展开更多
Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling...Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases （MAPKs）. As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity （long-term potentiation and long-term depression） and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor （NMDAR） stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.展开更多
目的:比较药物联合预处理和单种药物预处理对沙土鼠脑缺血再灌注损伤的脑保护作用。方法:沙土鼠43只,随机分为正常对照组(A)、缺血损伤组(B)、利多卡因及异丙酚联合预处理组(C)、异丙酚预处理组(D),利多卡因预处理组(E),C、D、E预处理...目的:比较药物联合预处理和单种药物预处理对沙土鼠脑缺血再灌注损伤的脑保护作用。方法:沙土鼠43只,随机分为正常对照组(A)、缺血损伤组(B)、利多卡因及异丙酚联合预处理组(C)、异丙酚预处理组(D),利多卡因预处理组(E),C、D、E预处理组在脑缺血前24 h分别予利多卡因30 m g/kg及异丙酚100 m g/kg、异丙酚100 m g/kg、利多卡因30 m g/kg腹腔注射,对照组7只,余每组为9只,观察指标为SOD(超氧化物岐化酶)、G SH(谷光甘肽)的活性及M DA(丙二醛)、LDH(乳酸脱氢酶)、CPK(肌磷酸激酶)含量。每组随机取一左大脑皮层的1 mm×1 mm组织块作电镜,观察脑组织超微结构的改变。结果:各个药物预处理组的M DA、LDH、CPK的含量低于缺血损伤组(P<0.05,P<0.01或P<0.001),而SOD、G SH的活性高于缺血损伤组(P<0.05,P<0.01或P<0.001),而各个预处理组比较利多卡因及异丙酚联合预处理比单独预处理显示出来更好的保护作用(P<0.05或P<0.01)。与缺血再灌注组比较,各个药物预处理组在电镜超微结构均有改善,以利多卡因及异丙酚联合预处理组的改善较为明显。结论:缺血前24 h予药物预处理对沙土鼠的脑缺血再灌注损伤均有不同程度的减轻作用,并以联合预处理组的效果最为显著。展开更多
文摘Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a continuous Rb administration method based on effect-site concentrations calculated by a pharmacokinetic/pharmacodynamics model during propofol, sevoflurane, and desflurane anesthesia. Methods: The 36 enrolled patients were equally divided into three groups (P;propofol, S;sevoflurane, and D;desflurane groups). After induction and administration of Rb 0.6 mg/kg, we calculated the simulated effect-site concentration at the point which the first twitch (%T1) recovered to > 0% and defined this as the Rb recovery concentration (Rbr.c.) level appropriate for continuous rocuronium administration. The continuous administration doses of Rb were adjusted to maintain Rbr.c. during surgery. The Rbr.c. and the recovery time at %T1 > 25% were recorded for each type of anesthesia. Results: Rbr.c. (μg/mL) for the P, S, and D groups were 1.54 ± 0.2, 1.24 ± 0.2, and 1.09 ± 0.2, respectively. Continuous administration doses (μg/kg/min) in the P, S, and D group were 6.7 ± 0.9, 5.2 ± 1.0, and 4.5 ± 0.8, respectively. Rbr.c. and continuous doses in the S and D groups were lower than the P group. Neuromuscular relaxations during surgery in the S and D groups were more strongly maintained than for the P group. There was also a significantly prolonged recovery duration for the %T1 > 25% in the D versus the other two groups (P < 0.05). Conclusion: Results showed that our continuous administration method was effective for maintaining sufficient muscle relaxation without excessively prolonged recovery effects for both sevoflurane and desflurane as well as propofol anesthesia.
文摘Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases （MAPKs）. As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity （long-term potentiation and long-term depression） and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor （NMDAR） stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.
文摘目的:比较药物联合预处理和单种药物预处理对沙土鼠脑缺血再灌注损伤的脑保护作用。方法:沙土鼠43只,随机分为正常对照组(A)、缺血损伤组(B)、利多卡因及异丙酚联合预处理组(C)、异丙酚预处理组(D),利多卡因预处理组(E),C、D、E预处理组在脑缺血前24 h分别予利多卡因30 m g/kg及异丙酚100 m g/kg、异丙酚100 m g/kg、利多卡因30 m g/kg腹腔注射,对照组7只,余每组为9只,观察指标为SOD(超氧化物岐化酶)、G SH(谷光甘肽)的活性及M DA(丙二醛)、LDH(乳酸脱氢酶)、CPK(肌磷酸激酶)含量。每组随机取一左大脑皮层的1 mm×1 mm组织块作电镜,观察脑组织超微结构的改变。结果:各个药物预处理组的M DA、LDH、CPK的含量低于缺血损伤组(P<0.05,P<0.01或P<0.001),而SOD、G SH的活性高于缺血损伤组(P<0.05,P<0.01或P<0.001),而各个预处理组比较利多卡因及异丙酚联合预处理比单独预处理显示出来更好的保护作用(P<0.05或P<0.01)。与缺血再灌注组比较,各个药物预处理组在电镜超微结构均有改善,以利多卡因及异丙酚联合预处理组的改善较为明显。结论:缺血前24 h予药物预处理对沙土鼠的脑缺血再灌注损伤均有不同程度的减轻作用,并以联合预处理组的效果最为显著。
