Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low‐dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose‐dependent inhibition of 4‐AP‐evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl ‐threo‐beta‐benzyl‐oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization‐induced increase in [Ca²⁺]_C but did not alter 4‐AP‐mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca_v2.2 (N‐type) and Ca_v2.1 (P/Q‐type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]_C caused by Ca²⁺ entry through presynaptic voltage‐dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades. Synapse 67:568–579, 2013 . © 2013 Wiley Periodicals, Inc.     

全身麻醉药物选择与老年手术患者预后:吸入麻醉还是静脉麻醉

背景 随着社会人口的老龄化,需要接受手术治疗的老年患者越来越多,麻醉管理对老年患者预后的影响值得关注. 目的 回顾吸入麻醉与静脉麻醉对老年手术患者预后的影响. 内容 对于心脏手术患者,吸入麻醉可能较丙泊酚静脉麻醉更有优势,但需进一步多中心、大规模临床研究证实.在对术后近期脑功能的影响方面,不同研究的结果差异较大,还无法得出明确结论;在对术后远期脑功能的影响方面,全身麻醉可能伴随术后痴呆风险增加,但还有待前瞻性研究证实.在对恶性肿瘤患者术后机体免疫功能的影响方面,丙泊酚静脉麻醉可能优于吸入麻醉,但其临床意义有待阐明;麻醉药物对恶性肿瘤患者肿瘤侵袭性及远期预后的影响值得进一步研究. 趋向 吸入麻醉与静脉麻醉对老年手术患者预后的影响,需要进一步的研究证实.     

七氟烷预处理对心脏瓣膜置换术患者炎性反应及心肌组织GSK3β、STAT5A表达的影响

目的 探讨七氟烷预处理对体外循环(cardiopulmonary bypass,CPB)下心脏瓣膜置换术患者心肌损伤的影响及潜在机制.方法 我院择期行心脏瓣膜置换术患者24例,完全随机分为2组(n=12):七氟烷预处理组和静脉麻醉对照组.麻醉维持:七氟烷预处理组于麻醉诱导插管后开始吸入1 MAC七氟烷20 min,再洗脱10 min;静脉麻醉对照组术中不吸入七氟烷.于麻醉诱导后即刻(TO)、主动脉开放2 h(T1)、6h(T2)、24 h(T3)、48 h(T4)采集桡动脉血并分离血浆,采用ELISA测定TNF-α、IL-6浓度,双向测流免疫法测定心肌肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTn Ⅰ)浓度及免疫抑制法测定磷酸肌酸同工酶(creatine phosphokinase isoenzyme,CK-MB)活性;于七氟烷洗脱后CPB前取右心耳组织,用Western blot检测糖原合成酶激酶3 β(glycogen synthase kinase 3 β,GSK3 β)、STAT5A磷酸化水平表达.结果 与TO比较,2组T1～T3时的cTn Ⅰ、TNF-α、IL-6浓度及CK-MB活性均升高(P＜0.05);与对照组比较,预处理组T1 ～ T2时的TNF-α、T1 ～ T3时的IL-6的浓度均降低(P＜0.05),而cTnI浓度、CK-MB活性2组差异无统计学意义(P＞0.05);与对照组比较,预处理组患者的右心耳组织的GSK3β、STAT5A磷酸化水平明显增高(P =0.046 9、0.005 8).结论 七氟烷预处理减轻心脏瓣膜置换术患者的炎症反应并且可能通过增加心肌组织GSK3β、STAT5A磷酸化表达介导心肌保护效应.     

Ongoing activity in trigeminal wide-dynamic range neurons is driven from the periphery

Ongoing activity of spinal trigeminal neurons is observed under various conditions and suggested to be responsible for ongoing headache. It can be spontaneous, i.e. arising intrinsically from the neuron, or the product of descending influences from other central neurons, or maintained by ongoing afferent input. The aim of the present study was to examine if ongoing activity of neurons in different subnuclei of the spinal trigeminal nucleus is driven from peripheral afferent input. Experiments were performed in Wistar rats anesthetized with isoflurane or Nembutal/urethane. Ongoing activity of single wide-dynamic range (WDR) neurons was recorded with carbon fiber glass microelectrodes in two subnuclei of the spinal trigeminal nucleus: oral (Sp5O) and caudal (Sp5C). Peripheral receptive fields were evaluated using von Frey filaments. Sp5O neurons received peripheral input from facial areas innervated by the mandibular branch of the trigeminal nerve. Units in Sp5C had receptive fields in the surgically exposed dura mater and in facial areas innervated by the ophthalmic and maxillary branch of the trigeminal nerve. Saline or the local anesthetic lidocaine was locally applied onto the exposed dura mater or microinjected into V3 (for Sp5O units) or V1/V2 (for Sp5C units) divisions of the trigeminal ganglion via the infraorbital channel. Local application of lidocaine onto the exposed dura caused mechanical insensitivity of dural receptive fields but not significant decrease in ongoing activity. Microinjection of lidocaine but not saline into the trigeminal ganglion was followed by a substantial decrease in both the receptive field size and the activity of the recorded WDR units. Mechanical insensitivity of receptive fields after trigeminal ganglion blockade was accompanied by the disappearance of ongoing activity. We conclude that the ongoing activity of WDR neurons in the spinal trigeminal nucleus, which may be indicative for processes of sensitization, is driven remotely by ongoing afferent input.     

Conformation and kinetic characteristics of interactions between local anesthetics and aqueous solutions of hydroxypropylmethylcellulose

Conformation and kinetic characteristics of the interactions of local anesthetics lidocaine (xycaine), tetracaine (dicaine), bupivacaine, and new RU-1117 compound with proven anesthetic activity with Visiton (1% hydroxypropylmethylcellulose in phosphate buffer) were studied. It was found that complex formation between the local anesthetics and hydroxypropylmethylcellulose is a time-dependent reversible process. The equilibrium is attained within 2.5–8.0 h and depends on the chemical nature of local anesthetic. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 563–567, May, 2007     

Critical care management of patients with severe burns and inhalational injury

Anaesthetists and critical care physicians involved in emergency care provision must be equipped with the adequate knowledge and skills to accurately assess and manage patients with severe burns. This summary aims to review the key principles in managing patients with severe burns including airway management, fluid resuscitation, sedation, burn care, analgesia and nutrition.