Evaluation of a simultaneous adsorption device for cytokines and platelet-neutrophil complexes in vitro and in a rabbit acute lung injury model

Yumiko Sekiya; Kaoru Shimada; Hiroshi Takahashi; Chisa Kuga; Shunsuke Komachi; Keishi Miwa; Toru Kotani

doi:10.1186/s40635-021-00414-7

Evaluation of a simultaneous adsorption device for cytokines and platelet-neutrophil complexes in vitro and in a rabbit acute lung injury model

Intensive Care Med Exp. 2021 Sep 27;9(1):49. doi: 10.1186/s40635-021-00414-7.

Authors

Yumiko Sekiya¹, Kaoru Shimada², Hiroshi Takahashi², Chisa Kuga², Shunsuke Komachi², Keishi Miwa², Toru Kotani³

Affiliations

¹ Medical Devices & Materials Research Lab., Advanced Materials Research Labs., Toray Industries, Inc., Shiga, Japan. yumiko.sekiya.d6@mail.toray.
² Medical Devices & Materials Research Lab., Advanced Materials Research Labs., Toray Industries, Inc., Shiga, Japan.
³ Department of Intensive Care Medicine, Showa University School of Medicine, Tokyo, Japan.

Abstract

Background: 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.

Results: 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 cmH₂O) 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 PaO₂/FIO₂ 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 PaCO₂ 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.

Conclusion: 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.

Keywords: ARDS; Blood purification; Cytokine; Platelet–neutrophil complex.