Department of Anaesthesiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
Br J Anaesth. 2012 Dec;109(6):887-96. doi: 10.1093/bja/aes303. Epub 2012 Sep 3.
Intraoperative hypotension is associated with increased risk of perioperative complications. The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) antagonist xenon (Xe) induces general anaesthesia without impairment of cardiac output and vascular resistance. Mechanisms involved in cardiovascular stability have not been identified.
Muscle sympathetic activity (MSA) (microneurography), sympathetic baroreflex gain, norepinephrine (NE) plasma concentration (high-performance liquid chromatography), anaesthetic depth (Narcotrend(®) EEG monitoring), and vital parameters were analysed in vivo during Xe mono-anaesthesia in human volunteers (n=8). In vitro, NE transporter (NET) expressing HEK293 cells and SH-SY5Y neuroblastoma cells were pre-treated with ketamine, MK-801, NMDA/glycine, or vehicle. Subsequently, cells were incubated with or without Xe (65%). NE uptake was measured by using a fluorescent NET substrate (n=4) or [(3)H]NE (n=6).
In vivo, Xe anaesthesia increased mean (standard deviation) arterial pressure from 93 (4) to 107 (6) mm Hg and NE plasma concentration from 156 (55) to 292 (106) pg ml(-1), P<0.01. MSA and baroreflex gain were unaltered. In vitro, ketamine decreased NET activity (P<0.01) in NET-expressing HEK293 cells, while Xe, MK-801, and NMDA/glycine did not. Xe reduced uptake in SH-SY5Y cells expressing NET and NMDA-Rs (P<0.01). MK-801 (P<0.01) and ketamine (P<0.01) also reduced NET activity, but NMDA/glycine blocked the effect of Xe on [(3)H]NE uptake.
In vivo, Xe anaesthesia does not alter sympathetic activity and baroreflex gain, despite increased mean arterial pressure. In vitro, Xe decreases the uptake of NE in neuronal cells by the inhibition of NET. This inhibition might be related to NMDA-R antagonism and explain increased NE concentrations at the synaptic cleft and in plasma, contributing to cardiovascular stability during Xe anaesthesia.
术中低血压与围手术期并发症风险增加有关。N-甲基-D-天冬氨酸（NMDA）受体（NMDA-R）拮抗剂氙（Xe）可诱导全身麻醉，而不损害心输出量和血管阻力。涉及心血管稳定性的机制尚未确定。
在人类志愿者（n=8）中进行 Xe 单一麻醉期间，进行肌肉交感神经活动（MSA）（微神经记录）、交感神经压力反射增益、去甲肾上腺素（NE）血浆浓度（高效液相色谱法）、麻醉深度（Narcotrend®EEG 监测）和生命参数的分析。在体外，用氯胺酮、MK-801、NMDA/甘氨酸或载体预处理表达 NE 转运体（NET）的 HEK293 细胞和 SH-SY5Y 神经母细胞瘤细胞。随后，用或不用 Xe（65%）孵育细胞。使用荧光 NET 底物（n=4）或[（3）H]NE（n=6）测量 NE 摄取。
体内 Xe 麻醉使平均动脉压从 93（4）mmHg 增加到 107（6）mmHg，NE 血浆浓度从 156（55）pg/ml 增加到 292（106）pg/ml，P<0.01。MSA 和压力反射增益没有改变。在体外，氯胺酮降低 NET 活性（P<0.01）在表达 NET 的 HEK293 细胞中，而 Xe、MK-801 和 NMDA/甘氨酸则没有。Xe 减少了表达 NET 和 NMDA-R 的 SH-SY5Y 细胞中的摄取（P<0.01）。MK-801（P<0.01）和氯胺酮（P<0.01）也降低了 NET 活性，但 NMDA/甘氨酸阻断了 Xe 对[（3）H]NE 摄取的影响。
体内 Xe 麻醉不会改变交感神经活动和压力反射增益，尽管平均动脉压升高。在体外，Xe 通过抑制 NET 来减少神经元细胞中 NE 的摄取。这种抑制可能与 NMDA-R 拮抗有关，并解释了 Xe 麻醉期间突触间隙和血浆中 NE 浓度的增加，有助于心血管稳定性。
