七氟醚后处理对局灶性脑缺血-再灌注损伤的保护作用

目的评价在缺血后期及再灌注早期吸入不同浓度的七氟醚行后处理对大鼠局灶性脑缺血-再灌注损伤的保护作用及其剂量依赖性。方法雄性SD大鼠50只,随机分为空白对照组、吸氧组和0.5、1.0、1.5MAC七氟醚后处理组,每组10只。采用大脑中动脉线栓法阻闭(middle cerebral artery occlusion,MCAO)120min后再灌注72h制备局灶性脑缺血模型。各七氟醚后处理组于再灌注即刻的前20min和后10min给予不同浓度七氟醚吸入。再灌注后的24、48和72h行神经功能评分(NDS),并于最后一次评分后测定脑梗死容积比。结果0.5、1.0和1.5MAC组的脑梗死容积比分别为0.39±0.03,0.31±0.03和0.24±0.03(P<0.05),明显小于对照组0.53±0.05(P<0.05)。吸氧组为0.51±0.05,与对照组比差异无统计学意义。各个时间点七氟醚后处理组NDS明显优于对照组和吸氧组。结论在局灶性脑缺血-再灌注的缺血后期和再灌注早期吸入0.5、1.0和1.5MAC七氟醚行后处理均具有脑保护作用,并呈现剂量依赖性。     

芬太尼联合七氟烷后处理对离体大鼠缺血/再灌注心功能的影响

目的 研究芬太尼联合七氟烷后处理对离体大鼠缺血/再灌注(ischemia/reperfusion,I/R)心脏心功能的影响.方法 建立离体大鼠心脏缺血40 min,再灌注120 min模型.根据再灌注开始10 min的不同处理,使用随机数字表法将实验动物随机分为4组(n=10):I/R对照组(Con),七氟烷后处理组(...     

缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响

目的探讨缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响。方法36只雄性SD 大鼠随机分为3组(n=12),对照组:即单纯缺血再灌注组;缺血后处理15s组(I-15 s组):大脑中动脉线栓阻闭(MCAO)90 min后,再灌注15 s,缺血15 s,反复3次;缺血后处理30 s组(I-30 s组):MCAO 90 min后,再灌注30 s,缺血30 s,反复3次。再灌注24 h后对所有动物行神经功能障碍评分(NDS),然后取大脑测定脑梗死容积。结果再灌注24 h后I-15 s和I-30 s组NDS与对照组比较差异无统计学意义(P>0.05)。再灌注24 h后脑梗死容积I-15s组为(271±97)mm3,I-30 s组为(217±85)mm3,小于对照组[(378±103)mm3](P<0.01),I-15 s和I-30 s组比较差异无统计学意义(P>0.05)。结论缺血后处理可减轻局灶性脑缺血再灌注大鼠脑的病理性损伤。     

线粒体KATP通道介导七氟醚预处理对大鼠的脑保护作用

目的 探讨七氟醚预处理对大鼠局灶性脑缺血-再灌注(IR)损伤的保护作用.方法 雄性SD大鼠60只随机均分为七氟醚预处理组(S组)、5-HD+七氟醚预处理组(HS组)、5-羟葵酸(5-HD)组(H组)、IR组和假手术组(C组).采用大脑中动脉线栓法缺血2 h、再灌注24 h制备大鼠局灶性脑IR模型(MCAO).S组于缺血前1 h经半密闭的吸入箱吸入七氟醚(呼气末浓度维持2.4%,持续30 min).HS、H组缺血前或七氟醚预处理前经尾静脉注射5-HD(10 mg/kg).再灌注24 h后用Zea Longa评分法进行神经功能缺陷评分,TTC染色法测大鼠脑梗死容积,免疫组化法测定大脑皮质Bcl-2和Bax蛋白表达.结果 与IR组比较,S组神经功能缺陷评分明显降低,脑梗死容积显著减少(P＜0.05);但HS、H、IR组神经功能缺陷评分和脑梗死容积差异无统计学意义.S组Bcl-2、Bax表达明显高于HS、H、IR组.结论 七氟醚预处理对局灶性脑IR损伤有一定程度的保护作用.其保护作用与mitoKATP通道的激活有关,并可能是通过调控凋亡相关基因Bcl-2和Bax的表达来实现.     

七氟烷后处理改善脑缺血大鼠的远期学习记忆

目的利用大鼠大脑中动脉闭塞模型(MCAO), 观察七氟烷后处理对脑缺血大鼠远期学习记忆能力的影响。方法雄性SD大鼠随机分为假手术组、对照组和七氟烷组, 每组28只, 七氟烷组在再灌注开始时吸入1.0最小肺泡浓度(MAC)七氟烷进行后处理。再灌注后28 d, 分别用氯化三苯基四氮唑(TTC)染色评估大鼠脑梗死容积, 用Morris水迷宫评估大鼠的空间学习记忆能力。组间比较采用单因素或双因素方差分析。结果再灌注28 d七氟烷组的脑梗死容积为37.59%, 明显小于对照组的46.21%(F=200.5, P<0.05)。水迷宫实验第5天七氟烷组的逃避潜伏期为16.25 s, 明显短于对照组的27.27 s(F=24.03, P<0.05)。结论七氟烷后处理可能通过减小脑梗死容积, 改善大鼠远期的空间学习和记忆能力。     

舒芬太尼预先给药对大鼠急性局灶性脑缺血-再灌注损伤的保护作用

目的 观察舒芬太尼预先给药对大鼠大脑中动脉栓塞(MCAO)所致局灶性脑缺血-再灌注损伤的保护作用.方法 40只雄性大鼠随机均分为四组,分别于缺血造模前腹腔注射舒芬太尼3μg/kg(S_1组)、6μg/kg(S_2组)、9μg/kg(S_3组)和等容积生理盐水为对照组(C组).给药后30 min,所有动物用右侧颈内动脉尼龙线线栓法致MCAO,120 min后恢复再灌注.再灌注24 h后记录神经功能障碍评分(NDS).随后取大脑切片行TTC染色,计算脑梗死容积百分比.结果 再灌注后24h,S_1组NDS评分明显高于其他三组(P<0.05),梗死容积百分比明显低于其他三组(P<0.05),S_2、S_3、C组间NDS评分和梗死容积百分比差异均无统计学意义.结论 舒芬太尼3μg/kg预先给药可明显减轻大鼠局灶性脑缺血-再灌注损伤.     

七氟烷预处理对大鼠脑缺血再灌注损伤近期和远期的影响

目的:观察七氟烷预处理对大鼠脑缺血再灌注损伤近期和远期的影响。方法:健康成年雄性SD大鼠40只,随机分为七氟烷预处理组(A组)和对照组(B组)各20只;七氟烷预处理组在缺血前吸入2%七氟烷30 min,利用大鼠大脑中动脉线栓阻闭法建立大鼠脑缺血再灌注损伤模型,阻断血流60 min后,去除线实现再灌注;1个月后进行动物恢复及神经认知行为学评估,包括旷场实验和水迷宫行为学检测。结果:缺血再灌注后,神经功能缺陷评分A组1分、2分、3分分别为4例、10例、6例,B组1分、2分、3分分别为0例,6例,14例,两组差异有统计学意义(P<0.05);A组缺血前血糖值为(5.84±0.35)mmol/L,缺血后上升为(8.94±0.46)mmol/L(P<0.05);B组缺血前血糖值为(5.76±0.42)mmol/L,缺血后上升为(12.9±0.69)mmol/L(P<0.05);两组间缺血后血糖值差异有统计学意义(P<0.05);A组旷场实验得分、中央格停留次数以及穿越平台次数分别为(34.83±0.25)分、(2.27±0.19)次和(4.67±0.34)次。B组组旷场实验得分、中央格停留次数以及穿越平台次数分别为(18.83±0.14)分、(1.35±0.11)次和(1.3±0.11)次,两组间差异均有统计学意义(P<0.05)。结论:七氟烷预处理对大鼠脑缺血再灌注损伤近期和远期均衡有一定保护作用。     

七氟醚后处理对大鼠肠缺血再灌注损伤的影响

目的 评价七氟醚后处理对大鼠肠缺血再灌注损伤的影响.方法 成年雄性SD大鼠36只,体重200 ～ 220 g,采用随机数字表法,将其分为4组(n=9)∶假手术组(Sham组)、肠缺血再灌注组(I/R组)、缺血后处理组(Ipo组)和七氟醚后处理组(Sevo组).I/R组、Ipo组Sevo组采用结扎肠系膜上动脉60 min,再灌注120min的方法制备肠缺血再灌注模型.Ipo组于再灌注即刻恢复血流30 s后再阻断30 s,重复3次行后处理.Sevo组于再灌注即刻吸入1.15％七氟醚30 min行后处理.再灌注120 min时,处死大鼠,取小肠组织,采用Chui评分法行病理学损伤评分;采用TUNEL法计算凋亡细胞密度;采用比色法检测MDA含量和SOD活性;采用Western blot法检测caspase-3蛋白表达.结果 与Sham组相比,I/R组、Sevo组和Ipo组病理学损伤评分、凋亡细胞密度和MDA含量均升高,SOD活性降低,caspase-3蛋白表达上调(P＜0.05);与I/R组相比,Sevo组和Ipo组病理学损伤评分、凋亡细胞密度和MDA含量均降低,SOD活性升高,caspase-3蛋白表达下调(P＜0.05);Sevo组和Ipo组病理学损伤评分、凋亡细胞密度、MDA含量、SOD活性和caspase-3蛋白表达比较差异无统计学意义(P＞0.05).结论 七氟醚后处理可通过减轻脂质过氧化反应和减少细胞凋亡,减轻大鼠肠缺血再灌注损伤,其保护效应与缺血后处理相似.     

PI3K/Akt信号通路在七氟醚后处理减轻大鼠局灶性脑缺血再灌注损伤中的作用

目的 评价磷脂酰肌醇3激酶/蛋白质丝氨酸苏氨酸激酶(PI3K/Akt)信号通路在七氟醚后处理减轻大鼠局灶性脑缺血再灌注损伤中的作用.方法 雄性SD大鼠64只,体重300～350 g,随机分为4组(n=16):局灶性脑缺血再灌注组(IR组)、七氟醚后处理组(SP组)、七氟醚后处理+Wortmannin组(SW组)和Wortmannin组(W组).采用电凝法阻断左侧大脑中动脉,夹闭双侧颈总动脉60 min恢复灌注的方法制备大鼠局灶性脑缺血再灌注模型.再灌注即刻SP组和SW组吸入2.5%七氟醚60 min,夹闭双侧颈总动脉30 min时SW组和W组股静脉输注Wortmannin 0.6 mg/kg.于再灌注24、48、72 h时行神经功能评分,最后1次评分后处死大鼠取脑,测定脑梗死体积,采用Western blot法检测左侧脑组织磷酸化Akt(p-Akt)和磷酸化Bad(p-Bad)的表达水平.结果 与IR组相比,SP组和SW组各时点神经功能评分升高,再灌注72 h时脑梗死体积比降低,脑组织p-Akt和p-Bad表达上调(P＜0.05),W组上述指标差异无统计学意义(P＞0.05);与SP组相比,SW组各时点神经功能评分降低,再灌注72 h时脑梗死体积比升高,脑组织p-Akt和p-Bad表达下调(P＜0.05).结论 PI3K/Akt信号通路激活后p-Bad表达上调可能参与了七氟醚后处理减轻大鼠局灶性脑缺血再灌注损伤的过程.     

七氟烷后处理对不同病程糖尿病大鼠离体心肌缺血再灌注损伤的影响

目的 评价七氟烷后处理对不同病程糖尿病大鼠离体心肌缺血再灌注损伤的影响.方法 清洁级健康雄性SD大鼠72只,体重200 ～ 240 g,采用随机数字法,将其随机分成6组(n=12):非糖尿病缺血再灌注组(I/R组)、非糖尿病七氟烷后处理组(I/R+ sevo组)、2周糖尿病缺血再灌注组(2DM组)、2周糖尿病七氟烷后处理组(2DM+ sevo组)、6周糖尿病缺血再灌注组(6DM组)、6周糖尿病七氟烷后处理组(6DM+ sevo组).制备离体心脏Langendorff灌注模型,各组经主动脉灌注K-H液,平衡灌注15 min后停灌30 min,I/R组、2DM组及6DM组均采用K-H液灌注75 min; I/R+ sevo组、2DM+ sevo组及6DM+ sevo组均采用含有3％七氟烷的K-H液灌注15 min,随后用K-H液继续灌注60 min.于平衡末、再灌注15和75 min时记录左室舒张末压、左室发展压、左心室压力上升最大速率、左心室压力下降最大速率以及心率.于再灌注15 min时取心肌组织,用Western blot法测定磷酸化Akt(p-Akt)和总Akt的表达,于再灌注75 min时采用TTC法测定心肌梗死体积,计算心肌梗死体积比.结果 与2DM组比较,2DM+ sevo组心功能改善,心肌梗死体积比减小,p-Akt表达上调(P＜0.05);与I/R组比较,I/R+ sevo组再灌注期间心功能改善,心肌梗死体积比减小,p-Akt表达上调(P＜0.05);与6DM组比较,6DM+ sevo组心功能指标、心肌梗死体积比及p-Akt表达差异无统计学意义(P＞0.05).结论 随着糖尿病病程进展,七氟烷后处理减轻大鼠心肌缺血再灌注损伤的作用减弱,可能与PI3K/Akt信号通路受损有关.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.