Microvascular endothelial function and leukocyte adhesion mechanisms during inhalational anesthesia

虽然循环血液动力学的改变被认为是吸入麻醉的主要后果，但其在微血管水平上的主要事件仍有待澄清。本研究测试了氟烷或七氟醚麻醉是否通过内皮细胞依赖机制引起白细胞粘附。大鼠分别用氟烷或七氟烷在100% O_2中麻醉，肺部机械通气。在微血管血流动力学监测下，通过活体视频显微镜记录肠系膜小静脉内白细胞的行为。为了研究白细胞滚动和粘附的机制，在使用抗p -选择素（MAb PB1.3）或抗细胞内粘附分子-1 （ICAM-1; MAb 1A29）的单克隆抗体预处理后，重复了这些研究。在基线麻醉条件下（1个最小肺泡浓度；MAC），七氟醚处理大鼠的静脉壁剪切率比氟烷处理大鼠高约2倍。在2MAC时，氟烷引起明显的小动脉结构和切变速率降低，同时静脉白细胞密度升高。七氟醚诱导白细胞滚动和黏附，PB1.3和1A29均能减弱白细胞滚动和黏附，但不影响细胞壁剪切速率。另一方面，PB1.3不能阻止卤代烷诱导的白细胞粘附，而1A29可以。综上所述，氟烷或七氟醚麻醉引起静脉白细胞滚动和粘连，可能增加白细胞依赖性组织损伤的风险。此外，七氟醚麻醉时，静脉内皮中p -选择素的上调在白细胞粘附中起着至关重要的作用，涉及ICAM-1的剪切依赖性粘附机制可能归因于氟烷诱导的粘附。观察表明硝普钠对麻醉诱导的粘连有抑制作用，这表明补充外源性NO可作为一种治疗策略来降低白细胞依赖性组织损伤的风险。与以往有关免疫系统和麻醉的研究相比，本研究的特点是对白细胞动力学进行体内分析。少

While altering circulatory hemodynamics has been considered a major consequence of inhalational anesthesia, its primary events at a microvascular level remain to be clarified. The present study tested whether halothane or sevoflurane anesthesia evoked leukocyte adhesion through endothelial cell-dependent mechanisms. Rats were anesthetized with halothane or sevoflurane in 100% O_2 and lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after pretreatment with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1 ; MAb 1A29). Under baseline anesthetic conditions (1 minimum alveolar concentration ; MAC), venular wall shear rates in the sevoflurane-treated rats were about 2-fold higher than those with halothane. At 2MAC,halothane cau … More sed a marked arteriolar construction and decreasing shear rates concurrent with an elevation of venular leukocyte density. Sevoflurane induced leukocyte rolling and adhesion, which were attenuated by PB1.3 as well as 1A29, without alterations in the wall shear rates. On the other hand, halothane-induced leukocyte adhesion was not prevented by PB1.3 but by 1A29. In conclusion, halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion, which may increase the risk of leukocyte-dependent tissue injury. In addition, P-selectin upregulation in venular endothelium plays a crucial role in the leukocyte adhesoion during sevoflurane anesthesia, shear-dependent adhesion mechanisms involving ICAM-1 is likely to be ascribable to the halothane-induced adhesion. The observation demonstrating the inhibitory effect of sodium nitroprusside on the anesthesia-induced adhesion suggests that supplement of exogenous NO serves as a therapeutic strategy to reduce a risk of leukocyte-dependent tissue injury. Compared with previous studies regarding immune system and anesthesia, our study is characterized by in vivo analysis of leukocyte dynamics. Less