Biomedical Engineering Program, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
J Appl Physiol (1985). 2023 Aug 1;135(2):239-250. doi: 10.1152/japplphysiol.00028.2023. Epub 2023 Jun 8.
Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (Nitrogen-saline), and inflammation (F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmHO); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia ( = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of F-fluorodeoxyglucose uptake was related to local Q/D ( < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy. Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.
肺灌注量和分布对于氧合以及潜在的急性呼吸窘迫综合征（ARDS）中的肺炎症和保护至关重要。然而，在 ARDS 之前，灌注模式及其与炎症的关系尚不清楚。我们的目的是在不同生理条件下，通过不同的全身炎症和呼气末正压（PEEP）水平，评估大型动物早期肺损伤时的灌注/密度比和空间灌注-密度分布，并将其与炎症相关联。绵羊进行保护性通气（16-24 小时），并用氮-生理盐水进行肺密度、肺毛细血管灌注（Nitrogen-saline）和炎症（F-氟脱氧葡萄糖）的正电子发射和计算机断层扫描成像。我们研究了四种情况：允许性肺不张（PEEP = 0 cmH2O）；以及 ARDSNet 低拉伸 PEEP 设置策略，伴仰卧位中或轻度内毒素血症，和俯卧位轻度内毒素血症。在所有组中，ARDS 前的灌注/密度异质性增加。灌注向密度的再分布取决于通气策略和内毒素血症水平，在轻度内毒素血症时产生比中度内毒素血症更多的肺不张（= 0.010），而基于氧合的 PEEP 设置策略则相反。F-氟脱氧葡萄糖摄取的空间分布与局部 Q/D 相关（Q/D 组相互作用<0.001）。中度内毒素血症导致正常低密度肺中灌注明显减少/为零，而氮-生理盐水灌注表明非依赖性毛细血管闭塞。俯卧位动物的灌注明显均匀分布于密度。在动物的保护性通气的 ARDS 前阶段，肺灌注不均匀地向密度重新分布。这与炎症增加、非依赖性毛细血管闭塞以及根据内毒素血症水平和通气策略的肺去募集易感性有关。在全身内毒素血症和保护性潮气量机械通气的最初 16-24 小时内，灌注的再分布并不遵循肺密度的再分布。在不同的内毒素血症水平下，相同的基于氧合的呼气末正压（PEEP）设置策略可能导致不同的灌注再分布、PEEP 值和肺充气，从而使肺生物力学条件恶化。在急性肺损伤早期，区域性灌注与组织密度比与中性粒细胞炎症增加、非依赖性毛细血管闭塞和肺去募集的易感性相关，这可能标记和/或驱动肺损伤。
