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俯卧位可降低实验性急性呼吸窘迫综合征中 [C](R)-PK11195 正电子发射断层扫描测量的急性肺炎症。

Prone position decreases acute lung inflammation measured by [C](R)-PK11195 positron emission tomography in experimental acute respiratory distress syndrome.

机构信息

Service de Médecine Intensive - Réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.

Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, CNRS, Inserm, CREATIS UMR 5220, U1294, Villeurbanne, France.

出版信息

J Appl Physiol (1985). 2023 Feb 1;134(2):467-481. doi: 10.1152/japplphysiol.00234.2022. Epub 2023 Jan 12.

DOI:10.1152/japplphysiol.00234.2022
PMID:36633865
Abstract

Whether prone positioning (PP) modulates acute lung inflammation by the modulation of biomechanical forces of ventilator-induced lung injuries (VILIs) remains unclear. We aimed to demonstrate that PP decreases acute lung inflammation in animals with experimental acute respiratory distress syndrome (ARDS). Animals were under general anesthesia and protective ventilation (tidal volume 6 mL·kg, PEEP 5 cmHO). ARDS was induced by intratracheal instillation of chlorohydric acid. Animals were then randomized to PP, or to supine position (SP). After 4 h, a positron emission tomography (PET) acquisition with C-PK11195 was performed coupled with computerized tomography (CT) acquisitions, allowing the CT quantification of VILI-associated parameters. C-PK11195 lung uptake was quantified using pharmacokinetic multicompartment models. Analyses were performed on eight lung sections distributed along the antero-posterior dimension. Six animals were randomized to PP, five to SP (median [Formula: see text]/[Formula: see text] [interquartile range]: 164 [102-269] mmHg). The normally aerated compartment was significantly redistributed to the posterior lung regions of animals in PP, compared with SP. Dynamic strain was significantly increased in posterior regions of SP animals, compared with PP. After 4 h, animals in PP had a significantly lower uptake of C-PK11195, compared with SP. C-PK11195 regional uptake was independently associated with the study group, dynamic strain, tidal hyperinflation, and regional respiratory system compliance in multivariate analysis. In an experimental model of ARDS, 4 h of PP significantly decreased acute lung inflammation assessed with PET. The beneficial impact of PP on acute lung inflammation was consecutive to the combination of decreased biomechanical forces and changes in the respiratory system mechanics. Prone position decreases acute lung macrophage inflammation quantified in vivo with C-PK11195 positron emission tomography in an experimental acute respiratory distress syndrome. Regional macrophage inflammation is maximal in the most anterior and posterior lung section of supine animals, in relation with increased regional tidal strain and hyperinflation, and reduced regional lung compliance.

摘要

无论是俯卧位(PP)通过调节呼吸机引起的肺损伤(VILI)的生物力学力来调节急性肺炎症,目前尚不清楚。我们旨在证明 PP 可降低实验性急性呼吸窘迫综合征(ARDS)动物的急性肺炎症。动物处于全身麻醉和保护性通气(潮气量 6mL·kg,呼气末正压 5cmH2O)下。通过气管内滴注盐酸诱导 ARDS。然后,动物被随机分配到 PP 或仰卧位(SP)。4 小时后,进行正电子发射断层扫描(PET)与计算机断层扫描(CT)采集的 [C](R)-PK11195 采集,允许 CT 量化与 VILI 相关的参数。使用药代动力学多室模型定量[C](R)-PK11195 的肺摄取。对沿前后方向分布的八个肺段进行分析。六只动物被随机分配到 PP,五只动物被随机分配到 SP(中位数 [Formula: see text]/[Formula: see text] [四分位间距]:164 [102-269]mmHg)。与 SP 相比,PP 中的正常充气隔室明显重新分布到后肺区。与 PP 相比,SP 动物的后部区域的动态应变明显增加。4 小时后,与 SP 相比,PP 动物的 [C](R)-PK11195 摄取明显降低。[C](R)-PK11195 区域摄取在多变量分析中与研究组、动态应变、潮气量过度充气和区域呼吸系统顺应性独立相关。在 ARDS 的实验模型中,4 小时的 PP 明显降低了用 PET 评估的急性肺炎症。PP 对急性肺炎症的有益影响与减少生物力学力和呼吸系统力学变化有关。在实验性急性呼吸窘迫综合征中,与仰卧位动物的最前和最后肺段相比,俯卧位可减少体内 [C](R)-PK11195 正电子发射断层扫描定量的急性肺巨噬细胞炎症,与区域潮气量应变和过度充气增加以及区域肺顺应性降低有关。

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