Modeling Ventilator-Induced Lung Injury and Neutrophil Infiltration to Infer Injury Interdependence
Modeling Ventilator-Induced Lung Injury and Neutrophil Infiltration to Infer Injury Interdependence
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DOI：
10.1007/s10439-023-03346-3
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发表时间：
2023-08-17
影响因子：
3.8
通讯作者：
Smith，Bradford J. J.
中科院分区：
文献类型：
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作者：
Mattson，Courtney L. L.;Smith，Bradford J. J.
急性呼吸窘迫综合征（ARDS）和呼吸机引起的肺损伤（VILI）是异质性疾病。这些异质性的时空演化是复杂的，很难阐明驱动其进展的机制。通过之前的定量分析，我们探索了实验性 VILI 中细胞损伤和中性粒细胞浸润的分布，发现 VILI 进展的特点是在准随机位置形成新损伤和现有损伤簇的扩展。中性粒细胞浸润的分布与细胞损伤进展无关，提示存在全身反应。为了进一步研究 VILI 的动力学，我们开发了一种新颖的计算模型，使用随机方法模拟损伤（细胞损伤进展和中性粒细胞浸润）。对模型参数进行优化以拟合实验数据表明，随着机械通风模式的危害性变得更大，现有受损区域和新受损区域之间的相互依赖性的范围和强度都会增加。细胞损伤的相互依赖性可归因于机械束缚力，而中性粒细胞的相互依赖性可能归因于更远距离的细胞信号传导途径。
Acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) are heterogeneous conditions. The spatiotemporal evolution of these heterogeneities is complex, and it is difficult to elucidate the mechanisms driving its progression. Through previous quantitative analyses, we explored the distributions of cellular injury and neutrophil infiltration in experimental VILI and discovered that VILI progression is characterized by both the formation of new injury in quasi-random locations and the expansion of existing injury clusters. Distributions of neutrophil infiltration do not correlate with cell injury progression and suggest a systemic response. To further examine the dynamics of VILI, we have developed a novel computational model that simulates damage (cellular injury progression and neutrophil infiltration) using a stochastic approach. Optimization of the model parameters to fit experimental data reveals that the range and strength of interdependence between existing and new damaged regions both increase as mechanical ventilation patterns become more injurious. The interdependence of cellular injury can be attributed to mechanical tethering forces, while the interdependence of neutrophils is likely due to longer-range cell signaling pathways.