Microvascular endothelial function and leukocyte adhesion mechanisms during inhalational anesthesia

虽然改变循环血流动力学已被认为是吸入麻醉的主要后果，但其在微血管水平的主要事件仍有待阐明。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黏附。用氟烷或七氟醚在100%氧气中麻醉大鼠，机械通气。在监测微血管血流动力学的情况下，通过活体视频显微镜记录肠系膜小静脉中的白细胞行为。为了研究白细胞滚动和黏附的机制，在用抗P-选择素的单抗(MAb PB1.3)或抗细胞内黏附分子-1(ICAM-1；MAb 1A29)的单抗预处理后，重复这些研究。在基线麻醉条件下(1最低肺泡浓度；MAC)，七氟醚组大鼠的静脉壁剪切率约为氟烷组的2倍。在2MAC，氟烷CAU…更多的原因是有明显的小动脉结构和切变率的降低，同时静脉血白细胞密度升高。七氟醚引起的白细胞卷曲和粘连可被PB1.3和1A29减弱，但不改变壁切变率。另一方面，PB1.3不能阻止氟烷诱导的白细胞黏附，但1A29可阻止其黏附。综上所述，氟烷或七氟醚麻醉会导致静脉内白细胞卷曲和粘连，这可能增加白细胞依赖性组织损伤的风险。此外，在七氟醚麻醉过程中，静脉内皮细胞P-选择素的上调在白细胞黏附中起着关键作用，涉及ICAM-1的剪切依赖性黏附机制可能归因于氟烷诱导的黏附。硝普钠对麻醉诱导的粘连的抑制作用的观察表明，补充外源性NO可以作为一种治疗策略，以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，我们的研究以体内白细胞动力学分析为特征。较少

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