脓毒症心肌损伤的线粒体机制

背景 脓毒症是机体对感染的反应失调而导致危及生命的多器官功能障碍.虽然目前针对脓毒症有一些治疗措施,但脓毒症和脓毒症休克仍是导致危重症患者死亡的首要原因.心肌损伤是脓毒症的常见并发症,会导致左室和右室泵功能衰竭.参与脓毒症心肌损伤的物质和机制很多,包括毒素、细胞因子、一氧化氮、补体激活、凋亡和能量代谢紊乱等.然而,关于脓毒症心肌损伤的潜在分子机制尚未完全清楚.目的 讨论可能导致脓毒症心肌损伤线粒体功能异常的机制.内容 关于脓毒症心肌损伤研究比较多的是线粒体功能异常,目前研究认为线粒体功能损伤涉及许多机制,导致线粒体能量耗竭,最终导致心肌损伤.而对于线粒体功能的损伤和修复机制仍存在争议.趋向 关于脓毒症的研究不断升温,新的研究工具的出现为将来有效的特异性治疗方法的出现奠定了基础.     

脓毒症与线粒体损伤

线粒体是细胞的能量供应站、钙离子浓度的调节器、细胞死亡的执行者。脓毒症中细菌毒素的直接损害、免疫损害、氧自由基损害使线粒体的结构和功能发生改变,进而引起线粒体钙超载、呼吸功能障碍、凋亡、DNA损伤,最终使ATP合成受阻,细胞能量供应不足;凋亡调控系统激活,发生细胞凋亡。     

脓毒症与线粒体损伤

线粒体是细胞的能量供应站、钙离子浓度的调节器、细胞死亡的执行者。脓毒症中细菌毒素的直接损害、免疫损害、氧自由基损害使线粒体的结构和功能发生改变，进而引起线粒体钙超载、呼吸功能障碍、凋亡、DNA损伤，最终使ATP合成受阻．细胞能量供应不足；凋亡调控系统激活，发生细胞凋亡。     

线粒体质量控制系统在脓毒症相关性脑病中作用的研究进展

脓毒症相关性脑病是脓毒症最常见的中枢神经系统并发症,可导致患者远期神经功能异常、预后不良,目前尚无有效的防治策略。线粒体功能障碍是脓毒症相关性脑病的关键病理机制之一,已成为该领域研究热点。线粒体分裂融合、线粒体生物发生、线粒体自噬及线粒体运输等构成了线粒体质量控制系统,进而调节线粒体功能。因此,线粒体质量控制系统在脓毒症相关性脑病发生发展中具有重要作用。本文总结线粒体质量控制系统的主要调控机制及在脓毒症相关性脑病中的研究进展,并探讨线粒体质量控制系统在脓毒症相关性脑病评估和防治中的潜在价值。     

创面脓毒症大鼠组织ATP含量及合成酶活性的变化

目的：探讨烧伤后创面脓毒症对组织能量合成的影响。方法：60只背部30%Ⅲ度烫伤大鼠随机分为单纯烫伤组和刨面脓毒症组,创面脓毒症组大鼠创面涂以1×10~9 cfu/ml的铜绿假单胞菌观察伤后96h内心、肝、骨骼肌的ATP的含量及合成酶活性变化,同时电镜观察组织超微结构的相应改变。结果：伤后早期心肌、肝脏、骨骼肌细胞内ATP含量及合成酶活性均明显下降,此后单纯烫伤组逐渐恢复,至伤后96h脓毒症组大鼠ATP含量及合成酶活性明显低于对照组,并有与此相对应的线粒体数量和形态结构的改变。结论：烧伤后发生创面脓毒症时机体重要器官的线粒体结构损伤严重,组织ATP含量及合成酶活性明显下降,ATP合成不足加重了能量代谢的紊乱状况,线粒体的早期损伤可能是导致代谢紊乱的病理基础。     

睡眠障碍对机体免疫功能及脓毒症发生发展的影响

背景 神经免疫内分泌系统在脓毒症发生发展的过程中发挥着关键的作用,而睡眠障碍显著影响机体神经免疫系统的功能.不同类型睡眠障碍导致的机体免疫功能紊乱在脓毒症研究中受到越来越多的关注. 目的 系统阐述不同类型睡眠障碍对机体免疫功能的调控及对脓毒症发生发展的影响,为进一步完善脓毒症的神经-免疫-内分泌治疗提供防治新策略. 内容 综述睡眠障碍的类型和其对免疫功能及脓毒症发生发展的基础与临床研究进展. 趋向 睡眠障碍是目前普遍存在且严重影响人类健康的社会问题,由此引起的神经免疫内分泌功能障碍导致脓毒症患者预后不佳,神经-免疫-内分泌调节将开启脓毒症治疗的新靶向.     

斑点追踪技术评估脓毒症心肌功能障碍研究进展

脓毒症心肌功能障碍（SMD）是脓毒症器官损害的特异性表现。早期识别和干预可显著改善SMD患者预后。超声斑点追踪成像（STI）可准确量化SMD患者心肌舒缩功能,提高诊断SMD准确率。本文对STI评估SMD研究进展进行综述。     

线粒体膜通透性转换孔与心肌缺血-再灌注损伤的研究进展

<正>缺血性心脏病发病率不断上升,成为全世界致死和致残的首要疾病,严重威胁人类的健康。随着经皮腔内冠脉血管成形术、心脏动脉搭桥术、溶栓等技术的广泛应用,缺血性心脏病的死亡率明显地下降,然而有时候缺血后再灌注,不仅不能使缺血的心肌功能恢复,反而加重心肌的功能障碍和结构损伤,称为心肌缺血-再灌注损伤。而近些年来,线粒体膜通透性转换孔(mitochondrial permeability transition pore,     

脓毒症所致脑功能障碍的研究进展

正脓毒症和感染性休克第三版国际共识(脓毒症3.0)定义脓毒症是机体对感染反应失调而导致威胁生命的器官功能障碍,在其发病过程中常常伴随各种器官功能障碍,尤其是大脑[1]。脓毒症所致脑功能障碍(sepsis-induced brain dysfunction, SIBD)是指非中枢神经系统感染的脓毒症所致的弥漫性脑功能障碍,过去被称为"脓毒症相关性脑病(sepsis-associated encephalopathy, SAE)""感染中毒性     

线粒体质量控制在脓毒症急性肾损伤中作用机制的研究进展

脓毒症急性肾损伤临床常见，发病率和病死率高。线粒体功能障碍引起的肾小管细胞死亡是其发病机制之一。线粒体质量控制失调是导致线粒体功能障碍的主要原因。线粒体质量控制包括线粒体生物合成、线粒体融合/分裂和线粒体自噬。线粒体质量控制在脓毒症急性肾损伤中发挥着至关重要的作用，目前很多研究将线粒体质量控制作为脓毒症急性肾损伤的靶向治疗策略。因此，本文就线粒体质量控制在脓毒症急性肾损伤的相关研究进展进行综述，为临床防治脓毒症急性肾损伤提供参考和理论依据。     

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.