The effect of hyperoxia on inflammation and platelet responses in an ex vivo extracorporeal membrane oxygenation circuit.
Margaret R PassmoreKatrina K KiChris H H ChanTalvin LeeMahé BouquetEmily S WoodSainath RamanSacha RozencwajgAidan J C BurrellCharles I McDonaldDaman LangguthKiran ShekarMaximilian V MalfertheinerJohn F FraserJacky Y SuenPublished in: Artificial organs (2020)
Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2 ; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate- (P < .05) and thrombin receptor activating peptide-induced (P < .05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P = .013). Additionally, levels of the inflammatory chemokine interleukin-8 were elevated (P < .05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P = .002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro-inflammatory and oxidative stress response, however, exposure to supra-physiologic oxygen does not amplify that response. Extended-duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes.
Keyphrases
- extracorporeal membrane oxygenation
- oxidative stress
- acute respiratory distress syndrome
- diabetic rats
- immune response
- respiratory failure
- endothelial cells
- dna damage
- ischemia reperfusion injury
- mechanical ventilation
- early onset
- induced apoptosis
- high glucose
- signaling pathway
- preterm infants
- dendritic cells
- drug induced
- risk factors
- peripheral blood
- hydrogen peroxide
- single cell
- gestational age
- case control
- binding protein
- stress induced