Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response

Abstract

Background: Extracorporeal membrane oxygenation is a life-saving support for heart and/or lung failure patients. Despite technological advancement, abnormal physiology persists and has been associated with subsequent adverse events. These include thrombosis, bleeding, systemic inflammatory response syndrome and infection. However, the underlying mechanisms are yet to be elucidated. We aimed to investigate whether the different flow dynamics of extracorporeal membrane oxygenation would alter immune responses, specifically the overall inflammatory response, leukocyte numbers and activation/adhesion surface antigen expression. Methods: An ex vivo model was used with human whole blood circulating at 37°C for 6 hours at high (4 L/minute) or low (1.5 L/minute) flow dynamics, with serial blood samples taken for analysis. Results: During high flow, production of interleukin-1β (p < 0.0001), interleukin-6 (p = 0.0075), tumour necrosis factor-α (p = 0.0013), myeloperoxidase (p < 0.0001) and neutrophil elastase (p < 0.0001) were significantly elevated over time compared to low flow, in particular at 6 hours. While the remaining assessments exhibited minute changes between flow dynamics, a consistent trend of modulation in leukocyte subset numbers and phenotype was observed at 6 hours. Conclusion: We conclude that prolonged circulation at high flow triggers a prominent pro-inflammatory cytokine response and activates neutrophil granule release, but further research is needed to better characterize the effect of flow during extracorporeal membrane oxygenation.

COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review

“…The latter creates an inflammatory reaction, as already reported in the systemic inflammatory response syndrome, that involves leukocytes, platelet endothelial cells, intrinsic and extrinsic coagulation, cytokines, and complement system [23]. The result is an unbalance between pro-coagulant and anticoagulant factors, e.g., fibrinogen contributes to thrombus formation, while loss of high molecular vWF causes a bleeding tendency [24].…”

A narrative review of antithrombin use during veno-venous extracorporeal membrane oxygenation in adults: rationale, current use, effects on anticoagulation, and outcomes

“…Even though strict anticoagulation are not definitely accepted, guidelines and experts opinion suggest the higher anticoagulation level to be used. [33][34][35][36][37] A flowchart of the literature review and screening is shown in Figure 1. The data were extracted from 16 articles.…”

“…[39][40][41][42] As soon as ECMO blood flow commences, plasmatic proteins (in particular, coagulation factors), fibrinogen, and von Willebrand factor (vWF) are consumed by the cleavage by the ADAMTS-13 protein. 37,43 Fibrinogen may contribute to thrombus formation, while loss of high-molecular vWF may contribute to a bleeding tendency. 44 Platelets can be activated by multiple mechanisms: contact with biomaterial interface causes exposure of surface integrins and adhesion to the circuit; high shear stress, due to blood flow through the pump and oxygenator, induces activation of surface proteins, spreading the process, and exposing the phospholipids.…”

DataSheet_1.pdf

“…reduction was reported by Adrian et al, this was not observed by Graulich et al and partially observed by Ki et al (32,33,37). The discrepancies between the outcomes could be rationalized by the utilization of different ECMO technology, model setup, and blood flow rates.…”

“…In response to the continuous exposure to non-physiological conditions (e.g. flow rates and associated shear stress) and significant release of inflammatory mediators during ECMO (16,18,34,35,37,39,(65)(66)(67), cells of the endothelial lining are likely to convert into an activated state (68,69). This can subsequently elevate leukocyte adhesion [from phenotypic modulation (13,17,18,(34)(35)(36)] onto either the artificial surface of the ECMO circuit (23,24,70) or the endothelium itself (68,69), possibly acting as a consistent regulator of cell attachment in vivo.…”