心脏瓣膜置换术患者丙泊酚靶控输注维持浓度与意识消失浓度关系的研究

目的探讨BIS监测下心脏瓣膜置换术患者丙泊酚维持浓度与意识消失浓度之间的关系。方法择期开胸心脏瓣膜置换术患者30例,男8例,女22例,年龄39~64岁,麻醉诱导采用丙泊酚阶梯血浆靶控输注,初始血浆浓度(Cp)设定为1.0μg/ml,当预测效应室浓度(Ce)达0.5μg/ml时,每隔1分钟以0.3μg/ml递增Cp,患者意识消失(LOC)时静注舒芬太尼0.8~1.0μg/kg、罗库溴铵0.6~0.9mg/kg,当BIS达50时将Cp调至Ce水平,肌松满意后行气管插管。所有患者均在中低温心肺转流(CPB)下进行手术。记录患者入室后安静状态(基础值)(T_0)、LOC时(T_1)、BIS值达到50时(T_2)、切皮时(T_3)、劈胸骨时(T_4)、CPB开始时(T_5)、复温时(T_6)、CPB结束时(T_7)、关胸时(T_8)、术毕(T_9)时的MAP、HR、CVP、心排血量(CO)、每搏量(SV)、全身血管阻力(SVR)、BIS、丙泊酚Cp和Ce值。分析LOC时丙泊酚Ce值与围术期各变量相关性。结果相关分析中,患者LOC时丙泊酚Ce值与基础值CO、SV呈明显正相关(P0.01),与年龄呈明显负相关(P0.05);T_2~T_9时丙泊酚Ce值与LOC时Ce值呈明显正相关(P0.01);回归分析中,T_2~T_9时丙泊酚Ce值与LOC时Ce值呈明显正相关(P0.01)。结论在瓣膜置换术患者中,丙泊酚靶控输注维持浓度与LOC时浓度具有明显相关性,LOC时的丙泊酚Ce值可为维持浓度的调整提供一定参考依据。     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

Objective To investigate the role of cerebral opioid receptors in the protective effects of intracerebro-ventricular (ICV) morphine preconditioning (MPC) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Male SD rats weighing 320-370 g were used in this study. A needle was inserted through a surgically created hole into the cerebro-ventricle using a stereotactic instrument and fixed. Sixty male SD rats in which ICV needle was successfully placed without complication were randomly divided into 10 groups of 6 animals each. In group I sham operation was performed (S). In group]] myocardial I/R was produced (I/R) . In group Ⅲ (ischemic preconditioning), the animals were subjected to 3 episodes of 5 min myocardial ischemia at 5 min intervals before ischemia (IPC) . In group IV morphine was given ICV in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MPC). Three types of opioid receptor antagonists -nor-binaltorphimine (nor-BNI) (κ receptor antagonist), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) (μ receptor antagonist) and naltrindole (NTD) (S receptor antagonist) 15 nmol were given ICV in group V . VI and VIⅡI respectively at 10 min before MPC. In group VIII,IX and X , nor-BNI, CTOP and NTD 15 nmol were given ICV respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. At the end of 120 min, femoral venous blood samples were taken for determination of lactate dehydrogenase ( LDH) and creatine kinase (CK) activities and calcitonin gene-related peptide (CGRP) concentration. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct area (IA) . IA/AAR ratio was calculated. Results The size of IA was smaller and IA/AAR ratio lower and significantly less LDH and CK and more CGRP were released in group IPC and MPC ( group Ⅲ and IV) than in group I/R (group II ) . The protective effects of MPC were abolished by pretreatment with nor-BNI, CTOP and NTD. Conclusion Cerebral μ, k and δ opioid receptors are involved in the protective effects of ICV morphine preconditioning against myocardial I/R injury through CGRP released from peptidergic nerve fibers of heart.     

脊髓腺苷受体介导侧脑室吗啡预处理对大鼠缺血后心肌的保护作用

目的探讨脊髓腺苷受体在侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用中的介导作用以及与心肌缺血/再灌注损伤所引起的炎症反应的关系。方法健康♂SD大鼠54只,随机分为假手术组(Sham组)、对照组(CON组)、吗啡预处理组(MPC)、腺苷体阻断剂茶碱(theophylline,THE)+吗啡预处理组(MPC+THE组)、另设茶碱自身对照组,除茶碱自身对照组(6只)外,其他每组12只。每组观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积,心肌梗死面积以IS/AAR表示;免疫组化测定心肌组织细胞间黏附分子(ICAM-1)的表达水平。结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P<0.01),MPC+THE组分别明显低于CON组(P<0.01),高于MPC组(P<0.01),THE自身对照组与CON组相比差异无显著性(P>0.05);CON组心肌中的ICAM-1的表达水平明显高于Sham组(P<0.01),MPC组心肌组织中的ICAM-1的表达水平明显低于CON组(P<0.01),而MPC+THE组心肌组织中的ICAM-1的表达水平高于MPC组(P<0.01),低于CON组(P<0.01)。结论侧脑室吗啡预处理可以上调大鼠脊髓腺苷受体的激动水平,后者通过抑制心肌缺血/再灌注损伤的炎症反应,部分介导了侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用。     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

Objective To investigate the role of cerebral opioid receptors in the protective effects of intracerebro-ventricular (ICV) morphine preconditioning (MPC) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Male SD rats weighing 320-370 g were used in this study. A needle was inserted through a surgically created hole into the cerebro-ventricle using a stereotactic instrument and fixed. Sixty male SD rats in which ICV needle was successfully placed without complication were randomly divided into 10 groups of 6 animals each. In group I sham operation was performed (S). In group]] myocardial I/R was produced (I/R) . In group Ⅲ (ischemic preconditioning), the animals were subjected to 3 episodes of 5 min myocardial ischemia at 5 min intervals before ischemia (IPC) . In group IV morphine was given ICV in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MPC). Three types of opioid receptor antagonists -nor-binaltorphimine (nor-BNI) (κ receptor antagonist), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) (μ receptor antagonist) and naltrindole (NTD) (S receptor antagonist) 15 nmol were given ICV in group V . VI and VIⅡI respectively at 10 min before MPC. In group VIII,IX and X , nor-BNI, CTOP and NTD 15 nmol were given ICV respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. At the end of 120 min, femoral venous blood samples were taken for determination of lactate dehydrogenase ( LDH) and creatine kinase (CK) activities and calcitonin gene-related peptide (CGRP) concentration. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct area (IA) . IA/AAR ratio was calculated. Results The size of IA was smaller and IA/AAR ratio lower and significantly less LDH and CK and more CGRP were released in group IPC and MPC ( group Ⅲ and IV) than in group I/R (group II ) . The protective effects of MPC were abolished by pretreatment with nor-BNI, CTOP and NTD. Conclusion Cerebral μ, k and δ opioid receptors are involved in the protective effects of ICV morphine preconditioning against myocardial I/R injury through CGRP released from peptidergic nerve fibers of heart.     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

Objective To investigate the role of cerebral opioid receptors in the protective effects of intracerebro-ventricular (ICV) morphine preconditioning (MPC) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Male SD rats weighing 320-370 g were used in this study. A needle was inserted through a surgically created hole into the cerebro-ventricle using a stereotactic instrument and fixed. Sixty male SD rats in which ICV needle was successfully placed without complication were randomly divided into 10 groups of 6 animals each. In group I sham operation was performed (S). In group]] myocardial I/R was produced (I/R) . In group Ⅲ (ischemic preconditioning), the animals were subjected to 3 episodes of 5 min myocardial ischemia at 5 min intervals before ischemia (IPC) . In group IV morphine was given ICV in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MPC). Three types of opioid receptor antagonists -nor-binaltorphimine (nor-BNI) (κ receptor antagonist), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) (μ receptor antagonist) and naltrindole (NTD) (S receptor antagonist) 15 nmol were given ICV in group V . VI and VIⅡI respectively at 10 min before MPC. In group VIII,IX and X , nor-BNI, CTOP and NTD 15 nmol were given ICV respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. At the end of 120 min, femoral venous blood samples were taken for determination of lactate dehydrogenase ( LDH) and creatine kinase (CK) activities and calcitonin gene-related peptide (CGRP) concentration. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct area (IA) . IA/AAR ratio was calculated. Results The size of IA was smaller and IA/AAR ratio lower and significantly less LDH and CK and more CGRP were released in group IPC and MPC ( group Ⅲ and IV) than in group I/R (group II ) . The protective effects of MPC were abolished by pretreatment with nor-BNI, CTOP and NTD. Conclusion Cerebral μ, k and δ opioid receptors are involved in the protective effects of ICV morphine preconditioning against myocardial I/R injury through CGRP released from peptidergic nerve fibers of heart.     

c-Jun氨基末端激酶与心肌保护

作为促分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)超家族成员之一的c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)家族是与细胞增殖、分化或凋亡调控密切相关的细胞内信号转导通路.目前越来越多的报道证实了JNK信号途径具有促凋亡和抗凋亡的双重功能,这种双重功能受到细胞类型、刺激物的种类、剂量和持续时间以及胞内其他信号途径的影响.此综述主要探讨JNK在心肌缺血/再灌注(ischemic/reperfusion,I/R)损伤,缺血预处理(ischemic preconditioning,IPC)和缺血后处理中涉入机制及调节作用.     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 探讨脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 侧脑室置管成功的雄性SD大鼠60只,采用结扎冠状动脉左前降支30 min,再灌注120 min的方法制备心肌缺血再灌注模型.随机分为10组(n=6):假手术组(S组)、缺血再灌注组(IR组)、缺血预处理组(IPC组)、吗啡预处理组(MPC组)、nor-BNI组、CTOP组、NTD组、nor-BNI+MPC组、CTOP+MPC组和NTD+MPC组.IR组在缺血前30min时经5 min侧脑室输注生理盐水5 μl停止5 min,重复3次;IPC组在缺血前30 min时行缺血5 min,再灌注5min,反复3次.MPC组在缺血前30 min时经5 min侧脑室注射吗啡1 μg/kg(用生理盐水稀释到5μl),停止5 min,反复3次;IR组给予等容量生理盐水.nor-BNI组、CTOP组和NTD组分别在缺血前40 min时侧脑室注射nor-Binahorphimine(κ受体阻断剂)、D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(μ受体阻断剂)和Naltrindole(δ受体阻断剂),nor-BNI+MPC 组、CTOP+MPC组和NTD+MPC组于注射吗啡前10 min分别侧脑室注射3种阿片受体阻断剂,上述阿片受体阻断剂的剂量均为15 nmol.于再灌注120 min时采集股静脉血样,测定血清乳酸脱氢酶(LDH)、肌酸激酶(CK)的活性和血浆降钙素基因相关肽(CGRP)浓度,然后处死大鼠,取心肌组织,计算梗死区(IA)体积及IA与缺血危险区(AAR)体积的比值(IMAAR).结果 与IR组比较,IPC组和MPC组IA体积和IMAAR降低,血清LDH和CK的活性降低,血浆CGRP浓度升高(P<0.05或0.01);与MPC组比较nor-BNI+MP(=组、CTOP+MPC组和NTD+MPC组IA体积和IA/AAR升高,血清LDH 和CK的活性升高,血浆CGRP浓度降低(P<0.05或0.01).结论 脑λ、δ8和μ三种阿片受体均参与了侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤,其机制与支配心肌的肽能神经纤维释放CGRP有关.     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

Objective To investigate the role of cerebral opioid receptors in the protective effects of intracerebro-ventricular (ICV) morphine preconditioning (MPC) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Male SD rats weighing 320-370 g were used in this study. A needle was inserted through a surgically created hole into the cerebro-ventricle using a stereotactic instrument and fixed. Sixty male SD rats in which ICV needle was successfully placed without complication were randomly divided into 10 groups of 6 animals each. In group I sham operation was performed (S). In group]] myocardial I/R was produced (I/R) . In group Ⅲ (ischemic preconditioning), the animals were subjected to 3 episodes of 5 min myocardial ischemia at 5 min intervals before ischemia (IPC) . In group IV morphine was given ICV in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MPC). Three types of opioid receptor antagonists -nor-binaltorphimine (nor-BNI) (κ receptor antagonist), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) (μ receptor antagonist) and naltrindole (NTD) (S receptor antagonist) 15 nmol were given ICV in group V . VI and VIⅡI respectively at 10 min before MPC. In group VIII,IX and X , nor-BNI, CTOP and NTD 15 nmol were given ICV respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. At the end of 120 min, femoral venous blood samples were taken for determination of lactate dehydrogenase ( LDH) and creatine kinase (CK) activities and calcitonin gene-related peptide (CGRP) concentration. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct area (IA) . IA/AAR ratio was calculated. Results The size of IA was smaller and IA/AAR ratio lower and significantly less LDH and CK and more CGRP were released in group IPC and MPC ( group Ⅲ and IV) than in group I/R (group II ) . The protective effects of MPC were abolished by pretreatment with nor-BNI, CTOP and NTD. Conclusion Cerebral μ, k and δ opioid receptors are involved in the protective effects of ICV morphine preconditioning against myocardial I/R injury through CGRP released from peptidergic nerve fibers of heart.     

脑阿片受体在侧脑室注射吗啡预处理减轻大鼠心肌缺血再灌注损伤中的作用

Objective To investigate the role of cerebral opioid receptors in the protective effects of intracerebro-ventricular (ICV) morphine preconditioning (MPC) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Male SD rats weighing 320-370 g were used in this study. A needle was inserted through a surgically created hole into the cerebro-ventricle using a stereotactic instrument and fixed. Sixty male SD rats in which ICV needle was successfully placed without complication were randomly divided into 10 groups of 6 animals each. In group I sham operation was performed (S). In group]] myocardial I/R was produced (I/R) . In group Ⅲ (ischemic preconditioning), the animals were subjected to 3 episodes of 5 min myocardial ischemia at 5 min intervals before ischemia (IPC) . In group IV morphine was given ICV in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MPC). Three types of opioid receptor antagonists -nor-binaltorphimine (nor-BNI) (κ receptor antagonist), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) (μ receptor antagonist) and naltrindole (NTD) (S receptor antagonist) 15 nmol were given ICV in group V . VI and VIⅡI respectively at 10 min before MPC. In group VIII,IX and X , nor-BNI, CTOP and NTD 15 nmol were given ICV respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. At the end of 120 min, femoral venous blood samples were taken for determination of lactate dehydrogenase ( LDH) and creatine kinase (CK) activities and calcitonin gene-related peptide (CGRP) concentration. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct area (IA) . IA/AAR ratio was calculated. Results The size of IA was smaller and IA/AAR ratio lower and significantly less LDH and CK and more CGRP were released in group IPC and MPC ( group Ⅲ and IV) than in group I/R (group II ) . The protective effects of MPC were abolished by pretreatment with nor-BNI, CTOP and NTD. Conclusion Cerebral μ, k and δ opioid receptors are involved in the protective effects of ICV morphine preconditioning against myocardial I/R injury through CGRP released from peptidergic nerve fibers of heart.