Associations Between Systemic and Cerebral Inflammation in an Ovine Model of Cardiopulmonary Bypass. 氧气换气器横行动物模型中系统性和脑部炎症之间的关联。
Associations Between Systemic and Cerebral Inflammation in an Ovine Model of Cardiopulmonary Bypass.
发表日期：2023 Apr 01
作者：
Khalid Elsaafien, Jasmine M Sloan, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Sally G Hood, Song T Yao, Willian S Korim, Simon R Bailey, Alemayehu H Jufar, Rachel M Peiris, Rinaldo Bellomo, Lachlan F Miles, Clive N May, Yugeesh R Lankadeva
来源：
ANESTHESIA AND ANALGESIA
摘要：
手术中的炎症可能会导致经过体外循环（CPB）的心脏手术后出现术后神经认知障碍。然而，全身麻醉（GA）、手术部位损伤和CPB的相对贡献尚不清楚。我们在成年雌性绵羊中调查了GA和带或不带CPB的手术创伤期间前炎症和反炎症因子的时间轴和主要大脑皮层区域内小胶质细胞激活的程度（每组N = 5）。绵羊在清醒状态下、在GA和手术创伤期间以及带或不带CPB时进行研究。血浆肿瘤坏死因子-α（平均值[95％置信区间]，3.7 [2.5-4.9] vs 1.6 [0.8-2.3] ng/mL；P = 0.0004）和白细胞介素-6水平（4.4 [3.0-5.8] vs 1.6 [0.8-2.3] ng/mL；P = 0.029）在1.5小时时显著高于未接受CPB的动物，并在3小时时白细胞介素-6进一步增加（7.0 [3.7-10.3] vs 1.8 [1.1-2.6] ng/mL；P < 0.0001）。尽管大脑氧饱和度在整个CPB过程中得以保留，但在接受CPB的绵羊的额叶皮层中，小胶质细胞的圆形度更高，这表明明显的神经炎症（0.34 [0.32-0.37] vs 0.30 [0.29-0.32]; P = 0.029）。此外，在接受CPB的羊的顶叶（7.7 [6.5-8.9] vs 10.9 [9.4-12.5]; P = 0.001）和颞叶（7.8 [7.2-8.3] vs 9.9 [8.2-11.7]; P = 0.020）皮质内，小胶质细胞的分支较少。CPB增强了前炎症因子的释放，超出了GA和手术创伤的刺激范围。该全身炎症与3个主要大脑皮层区域内的小胶质细胞激活相关，其中额叶皮层具有吞噬性小胶质细胞表型，而顶叶和颞叶皮层都有炎性小胶质细胞表型。这些数据为大型动物模型中CPB诱导的神经炎症提供了直接的组织病理学证据，并提供了关于CPB诱导的大脑炎症如何引起术后神经认知障碍的更多机制数据。Copyright © 2023 International Anesthesia Research Society.
Intraoperative inflammation may contribute to postoperative neurocognitive disorders after cardiac surgery requiring cardiopulmonary bypass (CPB). However, the relative contributions of general anesthesia (GA), surgical site injury, and CPB are unclear.In adult female sheep, we investigated (1) the temporal profile of proinflammatory and anti-inflammatory cytokines and (2) the extent of microglia activation across major cerebral cortical regions during GA and surgical trauma with and without CPB (N = 5/group). Sheep were studied while conscious, during GA and surgical trauma, with and without CPB.Plasma tumor necrosis factor-alpha (mean [95% confidence intervals], 3.7 [2.5-4.9] vs 1.6 [0.8-2.3] ng/mL; P = .0004) and interleukin-6 levels (4.4 [3.0-5.8] vs 1.6 [0.8-2.3] ng/mL; P = .029) were significantly higher at 1.5 hours, with a further increase in interleukin-6 at 3 hours (7.0 [3.7-10.3] vs 1.8 [1.1-2.6] ng/mL; P < .0001) in animals undergoing CPB compared with those that did not. Although cerebral oxygen saturation was preserved throughout CPB, there was pronounced neuroinflammation as characterized by greater microglia circularity within the frontal cortex of sheep that underwent CPB compared with those that did not (0.34 [0.32-0.37] vs 0.30 [0.29-0.32]; P = .029). Moreover, microglia had fewer branches within the parietal (7.7 [6.5-8.9] vs 10.9 [9.4-12.5]; P = .001) and temporal (7.8 [7.2-8.3] vs 9.9 [8.2-11.7]; P = .020) cortices in sheep that underwent CPB compared with those that did not.CPB enhanced the release of proinflammatory cytokines beyond that initiated by GA and surgical trauma. This systemic inflammation was associated with microglial activation across 3 major cerebral cortical regions, with a phagocytic microglia phenotype within the frontal cortex, and an inflammatory microglia phenotype within the parietal and temporal cortices. These data provide direct histopathological evidence of CPB-induced neuroinflammation in a large animal model and provide further mechanistic data on how CPB-induced cerebral inflammation might drive postoperative neurocognitive disorders in humans.Copyright © 2023 International Anesthesia Research Society.