远隔缺血处理内源性心肌保护介质的研究进展

背景 作为远隔缺血处理(remote ischemic conditioning,RIPC)心肌保护最重要的效应因子,内源性介质已引起越来越多研究者的关注.目的 综述RIPC心肌保护作用介质的相关研究.内容 动物实验研究证实RIPC后收集动物的血液或冠脉流出液亦可对其他动物的心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)发挥明显的保护作用,但其机制尚未完全阐明.通过归纳目前的动物研究,作者从内源性保护介质的提出、成份鉴定及特性、细胞内信号机制进行系统描述.同时,概括来自人类的一些相关证据.趋势 需要进一步研究来明确内源性介质的主要效应成份,为心肌保护药物开发提供新的思路.     

吸入麻醉药后处理心肌保护作用机制的研究进展

背景 吸入麻醉药后处理(inhalational anesthetics postconditioning,APO)是指在缺血后冉灌注早期给予一定浓度吸入麻醉药处理.APO具有心肌保护作用,其作用机制目前尚未完全阐明.目的 对APO心肌保护作用机制的研究进展进行回顾和总结.内容 APO的心肌保护的信号转导机制与缺血后处...     

远隔处理——来自心脏之外的内源性心肌保护作用

背景 虽然缺血预处理(ischemia preconditioning,IPC)仍然是目前已知的最强大内源性心肌保护措施,但是各种原因其临床应用受到了限制.远隔于心脏之外的其他器官或组织经历短暂缺血后可使心肌对后继的长时间缺血更加耐受,即远隔缺血预处理(remote ischemic preconditioning,RIPC)的心肌保护作用.目前的研究已经将远隔处理的保护作用从单一的心肌保护领域扩展到了对全身众多器官或组织的保护作用中.在将远隔处理推荐作为临床工作的常规措施之前,仍需更多大规模的临床研究评估和优化其保护作用.目的 探讨远隔处理的心肌保护作用及研究进展.内容对远隔处理的发现、发展过程中的文献进行综述,并通过现有研究结果剖析远隔处理内在作用机制.趋向 远隔处理具有较光明的临床应用前景,通过对其作用机制和影响因素进行深入研究有助于获得更好的心肌保护干预策略.     

内质网应激与缺血后处理的心肌保护

内质网应激(endoplasmic reticulum stress,ERS)是细胞对各种伤害性刺激的适应性反应.在心肌缺血/再灌注(ischemia/reperfusion,I/R)过程中,过度的ERS引起心肌细胞凋亡导致心肌损伤.缺血后处理(ischemic postconditioning,I-postC)是心肌对抗I/R损伤的内源性保护现象,可通过多条信号转导途径发挥心肌保护作用,对ERS的调节是其重要方面.现将从ERS的角度探讨I-postC的心肌保护机制.     

内质网应激与缺血后处理的心肌保护

内质网应激(endoplasmic reticulum stress,ERS)是细胞对各种伤害性刺激的适应性反应.在心肌缺血/再灌注(ischemia/reperfusion,I/R)过程中,过度的ERS引起心肌细胞凋亡导致心肌损伤.缺血后处理(ischemic postconditioning,I-postC)是心肌对抗I/R损伤的内源性保护现象,可通过多条信号转导途径发挥心肌保护作用,对ERS的调节是其重要方面.现将从ERS的角度探讨I-postC的心肌保护机制.     

内质网应激与缺血后处理的心肌保护

内质网应激(endoplasmic reticulum stress,ERS)是细胞对各种伤害性刺激的适应性反应.在心肌缺血/再灌注(ischemia/reperfusion,I/R)过程中,过度的ERS引起心肌细胞凋亡导致心肌损伤.缺血后处理(ischemic postconditioning,I-postC)是心肌对抗I/R损伤的内源性保护现象,可通过多条信号转导途径发挥心肌保护作用,对ERS的调节是其重要方面.现将从ERS的角度探讨I-postC的心肌保护机制.     

挥发性麻醉药后处理保护缺血/再灌注心肌的研究进展

缺血后处理（ischemic postconditioning）是近年来提出的一种新的心肌保护方法,即心肌缺血后在长时间的再灌注之前,进行的数次短暂再灌注／缺血的循环。实验证明后处理对缺血心肌确有显著的保护作用。挥发性麻醉药后处理也可以发挥同样的保护效应,其机制比较复杂,远未阐明,现就其保护作用的机制作一综述。     

地氟烷在二尖瓣置换手术中对缺血再灌注心肌的保护作用

在心脏外科手术中心肌缺血再灌注(ischemia-reperfusion,I-R)损伤的防治是急需解决的问题。缺血预处理(ischemic preconditioning,IPC)具有心肌保护作用[1,2]。研究显示挥发性麻醉药也具有类似IPC的麻醉药预处理(anesthetic-induced preconditioning,APC)作用[3,4],能减轻I-R后     

挥发性麻醉药对缺血/再灌注肺损伤的保护机制

挥发性麻醉药对肺的作用目前尚有争议,但其抑制炎症反应的效应抗缺血/再灌注(I/R)损伤的保护性效应已在心肌、脑、肝、肾脏中得到证实.现就挥发性麻醉药对肺泡毛细血管的通透性、炎症因子、中性粒细胞的聚集及黏附分子的表达等的影响阐述挥发性麻醉药的肺保护的作用及机制.     

心肌缺血/再灌注损伤治疗新策略——迷走神经电刺激

背景 虽然缺血预处理(ischemic precondition,IPC)仍然是目前已知的最强大内源性心肌保护措施,但是因时机选择等原因其临床应用受到了极大的限制.大量动物实验证明,刺激迷走神经能够通过激活“胆碱能抗炎通路”、降低心肌交感神经兴奋性和抑制氧自由基的产生等作用机制,来减轻心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI).另外,也有少数随机对照临床研究证实了迷走神经刺激的心肌保护作用.目的 评价迷走神经刺激对心肌I/RI的保护作用.内容 包括迷走神经刺激的发现、发展,心肌保护作用的机制及其临床应用价值. 趋向 这一现象的发现为降低心肌I/RI提供了一个简单易行且费用低廉的措施.然而,在将迷走神经刺激推荐作为临床工作的常规措施之前,仍需进行更多大规模的临床研究,以评估和优化迷走神经刺激措施的保护作用.     

吸入麻醉药预处理对心肌缺血"第二保护窗"的作用机制

Volatile anesthetic preconditioning can elicit acute and delayed (also called as "second window") myocardial protection,and the latter may be more clinicaUy significant in decreasing the risk of myocardial ischemia/reperfusion injury for patientswith cardiovascular disease.The "second window" protection might be achieved by stimulating myocardium to trigger adenosine and nitric oxide release,passing through protein kinase C and nuclear factor-κB signal transduction pathways,activating the ATP-sensirive potassium channel and reactive oxygen species as the final effectors,presenting a delayed myocardial protective effect.This review summarizes the latest studies about volatile anesthetic preconditioning-induced "second window" protection.     

吸入麻醉药预处理对心肌缺血“第二保护窗”的作用机制

吸入麻醉药预处理对心肌缺血侑罐注损伤具有急性期和“第二保护窗”两个时间段的保护作用。“第二保护窗”起效缓慢而持久,临床上有充分的时间在手术前给予,能更方便有效地预防围术期心肌缺血的并发症。它可诱导一些触发因子如腺苷、一氧化氮的产生,通过信号转导通路蛋白激酶C、核因子-κB等,作用于ATP敏感性钾通道及活性氧族等终末效应离子通道或保护蛋白而发挥迟发性心肌保护。现就近年来关于吸入麻醉药预处理对心肌“第二保护窗”的作用机制作一综述。     

Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures

BACKGROUND: Volatile anesthetics are known to ameliorate experimental ischemic brain injury. A possible mechanism is inhibition of excitotoxic cascades induced by excessive glutamatergic stimulation. This study examined interactions between volatile anesthetics and excitotoxic stress. METHODS: Primary cortical neuronal-glial cultures were exposed to N-methyl-D-aspartate (NMDA) or glutamate and isoflurane (0.1-3.3 mM), sevoflurane (0.1-2.9 mM), halothane (0.1-2.9 mM), or 10 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial membrane potential were determined in the presence or absence of NMDA (0-200 microM). RESULTS: Volatile anesthetics reduced excitotoxin induced lactate dehydrogenase release by up to 52% in a dose-dependent manner. At higher concentrations, this protection was reversed. When corrected for olive oil solubility, the three anesthetics offered equivalent protection. MK-801 provided near-complete protection. Ca++ uptake was proportionally reduced with increasing concentrations of anesthetic but did not account for reversal of protection at higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells treated with volatile anesthetic had greater lactate dehydrogenase release than those left untreated. At protective concentrations, volatile anesthetics partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher concentrations, volatile anesthetics alone were sufficient to induce mitochondrial depolarization. CONCLUSIONS: Volatile anesthetics offer similar protection against excitotoxicity, but this protection is substantially less than that provided by selective NMDA receptor antagonism. Peak effects of NMDA receptor antagonism were observed at volatile anesthetic concentrations substantially greater than those used clinically.     

Effects of Volatile Anesthetics on N-methyl-d-aspartate Excitotoxicity in Primary Rat Neuronal-Glial Cultures

Background: Volatile anesthetics are known to ameliorate experimental ischemic brain injury. A possible mechanism is inhibition of excitotoxic cascades induced by excessive glutamatergic stimulation. This study examined interactions between volatile anesthetics and excitotoxic stress.

Methods: Primary cortical neuronal-glial cultures were exposed to N-methyl-d-aspartate (NMDA) or glutamate and isoflurane (0.1-3.3 mm), sevoflurane (0.1-2.9 mm), halothane (0.1-2.9 mm), or 10 [mu]m (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial membrane potential were determined in the presence or absence of NMDA (0-200 [mu]m).

Results: Volatile anesthetics reduced excitotoxin induced lactate dehydrogenase release by up to 52% in a dose-dependent manner. At higher concentrations, this protection was reversed. When corrected for olive oil solubility, the three anesthetics offered equivalent protection. MK-801 provided near-complete protection. Ca++ uptake was proportionally reduced with increasing concentrations of anesthetic but did not account for reversal of protection at higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells treated with volatile anesthetic had greater lactate dehydrogenase release than those left untreated. At protective concentrations, volatile anesthetics partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher concentrations, volatile anesthetics alone were sufficient to induce mitochondrial depolarization.     

Volatile anesthetics and cardiac function

All volatile anesthetics have been shown to induce a dose-dependent decrease in myocardial contractility and cardiac loading conditions. These depressant effects decrease myocardial oxygen demand and may, therefore, have a beneficial role on the myocardial oxygen balance during myocardial ischemia. Recently, experimental evidence has clearly demonstrated that in addition to these indirect protective effects, volatile anesthetic agents also have direct protective properties against reversible and irreversible ischemic myocardial damage. These properties have not only been related to a direct preconditioning effect but also to an effect on the extent of reperfusion injury. The implementation of these properties during clinical anesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. In the clinical practice, these effects should be associated with improved cardiac function, finally resulting in a better outcome in patients with coronary artery disease. The potential application of these protective properties of volatile anesthetic agents in clinical practice is the subject of ongoing research. This review summarizes the current knowledge on this subject.     

Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice

Reactive oxygen species (ROS) are central to cardiac ischemic and reperfusion injury. They contribute to myocardial stunning, infarction and apoptosis, and possibly to the genesis of arrhythmias. Multiple laboratory studies and clinical trials have evaluated the use of scavengers of ROS to protect the heart from the effects of ischemia and reperfusion. Generally, studies in animal models have shown such effects. Clinical trials have also shown protective effects of scavengers, but whether this protection confers meaningful clinical benefits is uncertain. Several IV anesthetic drugs act as ROS scavengers. In contrast, volatile anesthetics have recently been demonstrated to generate ROS in the heart, most likely because of inhibitory effects on cardiac mitochondria. ROS are involved in the signaling cascade for cardioprotection induced by brief exposure to a volatile anesthetic (termed "anesthetic preconditioning"). ROS, therefore, although injurious in large quantities, can have a paradoxical protective effect within the heart. In this review we provide background information on ROS formation and elimination relevant to anesthetic and adjuvant drugs with particular reference to the heart. The sources of ROS, the means by which they induce cardiac injury or activate protective signaling pathways, the results of clinical studies evaluating ROS scavengers, and the effects of anesthetic drugs on ROS are each discussed.     

Anesthetic protection against hepatic injury

In this review article, hepatocyte injury by volatile anesthetics, effects of anesthetics on hepatic perfusion, protection offered by either ischemic preconditioning or anesthetic preconditioning against hepatic ischemia-reperfusion injury and effects of anesthetics on sepsis-induced hepatic injury are discussed. Halothane poses significant risk of immunologically-mediated hepatocyte injury and disturbances of hepatic blood supply. Other modern volatile anesthetics such as isoflurane, sevoflurane and desflurane seem to have only minor risks. Several animal studies demonstrate that volatile anesthetics offer more protection against ischemia-reperfusion injury than intravenous anesthetics. On the contrary, intravenous anesthetics may be more protective against sepsis-induced hepatic injury than volatile anesthetics.     

吸入麻醉药心肌保护临床应用进展

大量的动物研究显示,除了对心肌的间接保护作用,吸入麻醉药还具有直接的对抗心肌缺血损伤的作用.这可能为临床提供了一种预防围手术期缺血心肌功能紊乱的技术.吸入麻醉药预处理、后处理技术应用于临床,可能会改善缺血/再灌注心肌的功能,并最终提高患者的愈后.吸入麻醉药心肌保护临床实验研究较少,现主要讨论近几年吸入麻醉药预处理临床应用的进展.     

Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo

BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. METHODS: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.     

Anaesthetic-induced myocardial preconditioning: fundamental basis and clinical implications

OBJECTIVE: Volatile halogenated anaesthetics offer a myocardial protection when they are administrated before a myocardial ischaemia. Cellular mechanisms involved in anaesthetic preconditioning are now better understood. The objectives of this review are to understand the anaesthetic-induced preconditioning underlying mechanisms and to know the clinical implications. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: volatile anaesthetic, isoflurane, halothane, sevoflurane, desflurane, preconditioning, protection, myocardium. DATA SYNTHESIS: Ischaemic preconditioning (PC) is a myocardial endogenous protection against ischaemia. It has been described as one or several short ischaemia before a sustained ischemia. These short ischaemia trigger a protective signal against this longer ischaemia. An ischemic organ is able to precondition a remote organ. It is possible to replace the short ischaemia by a preadministration of halogenated volatile anaesthetic with the same protective effect, this is called anaesthetic PC (APC). APC and ischaemic PC share similar underlying biochemical mechanisms including protein kinase C, tyrosine kinase activation and mitochondrial and sarcolemnal K(ATP) channels opening. All halogenated anaesthetics can produce an anaesthetic PC effect. Myocardial protection during reperfusion, after the long ischaemia, has been shown by successive short ischaemia or volatile anaesthetic administration, this is called postconditioning. Ischaemic PC has been described in humans in 1993. Clinical studies in human cardiac surgery have shown the possibility of anaesthetic PC with volatile anaesthetics. These studies have shown a decrease of postoperative troponin in patient receiving halogenated anaesthetics.