Sekiya Yumiko, Shimada Kaoru, Takahashi Hiroshi, Kuga Chisa, Komachi Shunsuke, Miwa Keishi, Kotani Toru
Medical Devices & Materials Research Lab., Advanced Materials Research Labs., Toray Industries, Inc., Shiga, Japan.
Department of Intensive Care Medicine, Showa University School of Medicine, Tokyo, Japan.
Intensive Care Med Exp. 2021 Sep 27;9(1):49. doi: 10.1186/s40635-021-00414-7.
Platelet-neutrophil complexes (PNCs) readily migrate into tissues and induce tissue damage via cytokine or other pathogenic factors release. These actions are involved in onset and progression of acute respiratory distress syndrome (ARDS). Thus, simultaneous removal of cytokines and activated neutrophils, including PNCs by blood purification may prevent development of ARDS and enhance drug effects. The goal of this study was to examine the effect of a newly developed adsorption column (NOA-001) that eliminates cytokines and activated neutrophils in a lung injury model.
Adsorption of cytokines, such as IL-8, IL-6 and HMGB-1, and PNCs was first measured in vitro. Lung injury was induced by HCl and lipopolysaccharide intratracheal infusion in rabbits ventilated at a low tidal volume (7-8 mL/kg) and PEEP (2.5 cmHO) for lung protection. Arterial blood gas, hematologic values, plasma IL-8, blood pressure and heart rate were measured, and lung damage was evaluated histopathologically in animals treated with 8-h direct hemoperfusion with or without use of NOA-001. The in vitro adsorption rates for IL-8, IL-6, HMGB-1, activated granulocytes and PNCs were 99.5 (99.4-99.5)%, 63.9 (63.4-63.9)%, 57.6 (57.4-62.1)%, 9.9 (-4.4-21.3)% and 60.9 (49.0-67.6)%, respectively. Absorption of PNCs onto fibers was confirmed microscopically. These adsorption effects were associated with several improvements in the rabbit model. In respiratory function, the PaO/FIO ratios at 8 h were 314 ± 55 mmHg in the NOA-001 group and 134 ± 41 mmHg in the sham group. The oxygenation index and PaCO at 8 h were 9.6 ± 3.1 and 57.0 ± 9.6 mmHg in the sham group and 3.0 ± 0.8 and 40.4 ± 4.5 mmHg in the NOA-001 group, respectively (p < 0.05). Blood pH at 8 h reached 7.18 ± 0.06 in the sham group, but was maintained at 7.36 ± 0.03 (within the normal range) in the NOA-001 group (p < 0.05). In lung histopathology, fewer hyaline membrane and inflammatory cells were observed in the NOA-001 group.
A column for simultaneous removal of cytokines and PNCs showed efficacy for improvement of pulmonary function in an animal model. This column may be effective in support of treatment of ARDS.
血小板-中性粒细胞复合物（PNCs）易于迁移至组织，并通过释放细胞因子或其他致病因子诱导组织损伤。这些作用参与急性呼吸窘迫综合征（ARDS）的发生和发展。因此，通过血液净化同时清除细胞因子和包括PNCs在内的活化中性粒细胞可能预防ARDS的发生并增强药物疗效。本研究的目的是在肺损伤模型中检测一种新开发的可清除细胞因子和活化中性粒细胞的吸附柱（NOA-001）的效果。
首先在体外测定细胞因子如白细胞介素-8（IL-8）、白细胞介素-6（IL-6）和高迁移率族蛋白B1（HMGB-1）以及PNCs的吸附情况。通过对采用低潮气量（7-8 mL/kg）和呼气末正压（PEEP，2.5 cmH₂O）通气的家兔气管内注入盐酸和脂多糖诱导肺损伤以保护肺脏。测量动脉血气、血液学指标、血浆IL-8、血压和心率，并对使用或未使用NOA-001进行8小时直接血液灌流的动物进行肺损伤的组织病理学评估。IL-8、IL-6、HMGB-1、活化粒细胞和PNCs的体外吸附率分别为99.5（99.4-99.5）%、63.9（63.4-63.9）%、57.6（57.4-62.1）%、9.9（-4.4-21.3）%和60.9（49.0-67.6）%。显微镜下证实PNCs吸附到纤维上。这些吸附作用与家兔模型中的多项改善相关。在呼吸功能方面，8小时时NOA-001组的动脉血氧分压/吸入氧分数（PaO₂/FiO₂）比值为314±55 mmHg，假手术组为134±41 mmHg。8小时时假手术组的氧合指数和动脉血二氧化碳分压（PaCO₂）分别为9.6±3.1和57.0±9.6 mmHg，NOA-001组分别为3.0±0.8和40.4±4.5 mmHg（p<0.05）。8小时时假手术组的血液pH值达到7.18±0.06，但NOA-001组维持在7.36±0.03（在正常范围内）（p<0.05）。在肺组织病理学方面，NOA-001组观察到的透明膜和炎性细胞较少。
一种可同时清除细胞因子和PNCs的吸附柱在动物模型中显示出改善肺功能的效果。该吸附柱可能对ARDS的治疗有辅助作用。
