Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale

Abstract

In order to assess mechanisms underlying inflammatory activation during extracorporeal circulation (ECC), several small animal models of ECC have been proposed recently. The majority of them are based on home-made, nonstandardized, and hardly reproducible oxygenators. The present study has generated fundamental information on the role of oxygenator of ECC in activating inflammatory signaling pathways on leukocytes, leading to systemic inflammatory response, and organ dysfunction. The present results suggest that experimental animal models of ECC used in translational research on inflammatory response should be based on standardized, reproducible oxygenators with clinical characteristics.

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

“…It is via these mechanisms, both within the vasculature and after trans-migration into the tissues that neutrophils act as the effectors of organ damage during ECMO [92]. The site of neutrophil activation during ECMO is likely to be multifocal, although in one experimental model of ECMO the fundamental role of the oxygenator was described [14]. During CPB, concentrations of neutrophil elastase, IL-8 and neutrophils are significantly elevated in bronchoalveolar lavage fluid; furthermore, these levels are correlated with the patients’ arterial partial pressure of oxygen (PaO 2 )/fraction of inspired oxygen (FiO 2 ) ratios [93].…”

“…Increased neutrophil margination into several tissues, particularly the lungs, has been described during ECMO, both in animal models and in neonates [14, 15, 30, 94]. Overall, neutrophil numbers increase after the initiation of extracorporeal circulation [95] and neutrophil function appears to be preserved [25, 28].…”

Oxidative Stress and Neonatal Respiratory Extracorporeal Membrane Oxygenation

“…Despite the use of biocompatible equipment, the interaction between biological fluids and the circuit activates both the coagulation cascade and the host inflammatory response (Tayama et al, 2000; Palatianos et al, 2003; Wiesenack et al, 2004; Thiara et al, 2010). The humoral and cell-mediated immune response triggers the release of pro-inflammatory cytokines (IL-1β, TNFα, and IFNβ), leading to endothelial damage, disrupted microcirculation and multi-organ dysfunction, in case of suboptimal compensatory anti-inflammatory response (Hocker et al, 1991; Hirthler et al, 1992; Depuydt et al, 1993; Plötz et al, 1993; Fortenberry et al, 1996; Adrian et al, 1998; Graulich et al, 2002; Golej et al, 2003; Mildner et al, 2005; Adib-Conquy and Cavaillon, 2009; Mcilwain et al, 2010; He et al, 2014; Shi et al, 2014; Rungatscher et al, 2015; Wang et al, 2015). The redox biology regulates the homeostasis of innate and adaptive immune response through ROS production.…”

Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass

“…The oxygenator has been proven to have an impact on the inflammatory response, leukocyte activation and organ dysfunction 154 . Any differences in impact on coagulation or inflammatory response between different brands of oxygenators has not been evaluated.…”