Damia Anna, Marongiu Ines, Spinelli Elena, Damarco Francesco, Uslenghi Clarissa, Rumi Giovanni Lorenzo, Battistin Michele, Lonati Caterina, Storaci Alessandra Maria, Lopez Gianluca, De Filippo Maria Rosaria, Madotto Fabiana, Banfi Cristina, Mallia Alice, Rosso Lorenzo, Vaira Valentina, Mauri Tommaso
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Intensive Care Med Exp. 2025 Jun 23;13(1):63. doi: 10.1186/s40635-025-00772-6.
The exclusion of one lung from ventilation or pulmonary artery perfusion triggers pathological mechanisms that can lead to lung injury. Although the final effect is similar for both insults, the underlying mechanisms may differ. Primary aim of this study was to compare severity of lung injury between non-ventilated (NVLI) and non-perfused (NPLI) lung injury. Secondary aims were to compare physiologic, imaging and proteomic signatures of NVLI vs NPLI.
Sedated and paralyzed healthy female piglets (weight = 36 ± 5 kg) were mechanically ventilated for 24 h after left pulmonary artery ligation (NPLI group, n = 11) or exclusion from ventilation of the left lung (NVLI group, n = 10). Physiological data including electrical impedance tomography imaging of regional ventilation and perfusion were collected. Histological scoring was performed blindly as well as proteomic analysis of broncho-alveolar lavage (BAL) fluids and lung tissue samples at the end of the experiment.
The left lung of both groups received similarly low fraction (< 20%) of blood flow. The left side of the NPLI group was characterized by ventilation distributed only to the dead space and high ventilation/perfusion compartments, while the left lung of the NVLI group was characterized by perfusion only to the shunt compartment. The left lung of the NVLI group showed severe pulmonary vascular dysfunction (pulmonary vascular resistance > 2000 dyne/s/cm), while the left lung of the NPLI group was ventilated with raising inspiratory stress (driving pressure > 20 cmHO at the end of the experiment and progressive decline in left lung compliance). The histologic lung injury score was higher for the left lung of the NVLI group compared to the left lung of the NPLI (left histological score: 10.3 ± 2.0 vs 6.4 ± 1.6, p < 0.0001), and pro-inflammatory alveolar cytokines were similarly more expressed in the left lung of the NVLI versus NPLI group (IL-1β: 418 ± 416 vs 53 ± 71, p < 0.001; IL-6: 406 ± 455 vs 99 ± 93, p = 0.036). Proteomic analysis showed signature specific for the two injuries, with two proteins, namely PRDX5 and DCTN1, being upregulated in NVLI left lung compared with the left NPLI lung. The right lung developed injury only in the NVLI group (right histological score: 5.5 ± 1.9 vs 3.0 ± 0.7, p < 0.001).
Lung injury is more severe in terms of lung histological score in the collapsed lung of the NVLI group and involves also contralateral areas. At the mechanistic level, NVLI has specific physiologic mechanisms like vascular dysfunction and inflammation and presents unique proteomic profile in comparison to NPLI.
一侧肺不进行通气或肺动脉灌注会触发可导致肺损伤的病理机制。尽管两种损伤的最终结果相似，但其潜在机制可能不同。本研究的主要目的是比较非通气性肺损伤（NVLI）和非灌注性肺损伤（NPLI）之间肺损伤的严重程度。次要目的是比较NVLI与NPLI的生理、影像学和蛋白质组学特征。
对镇静并麻痹的健康雌性仔猪（体重=36±5kg）在左肺动脉结扎后（NPLI组，n=11）或左肺不进行通气（NVLI组，n=10）的情况下进行24小时机械通气。收集包括区域通气和灌注的电阻抗断层成像在内的生理数据。在实验结束时，对组织学进行盲法评分，并对支气管肺泡灌洗（BAL）液和肺组织样本进行蛋白质组学分析。
两组的左肺均接受了相似的低血流量分数（<20%）。NPLI组左侧的特征是通气仅分布于死腔和高通气/灌注区域，而NVLI组的左肺特征是灌注仅分布于分流区域。NVLI组的左肺表现出严重的肺血管功能障碍（肺血管阻力>2000达因/秒/平方厘米），而NPLI组的左肺在吸气压力升高时进行通气（实验结束时驱动压力>20厘米水柱，左肺顺应性逐渐下降）。与NPLI组的左肺相比，NVLI组的左肺组织学肺损伤评分更高（左组织学评分：10.3±2.0对6.4±1.6，p<0.0001），并且促炎肺泡细胞因子在NVLI组左肺中的表达同样比NPLI组更明显（IL-1β：418±416对53±71，p<0.001；IL-6：406±455对99±93，p=0.036）。蛋白质组学分析显示了两种损伤的特异性特征，与NPLI组左肺相比，有两种蛋白质，即PRDX5和DCTN1，在NVLI组左肺中上调。仅在NVLI组右肺出现损伤（右组织学评分：5.5±1.9对3.0±0.7，p<0.001）。
就组织学肺损伤评分而言，NVLI组萎陷肺的肺损伤更严重，并且还累及对侧区域。在机制层面，与NPLI相比，NVLI具有血管功能障碍和炎症等特定的生理机制，并呈现出独特的蛋白质组学特征。
