Changes in Plasma Levels of Oxygen Radical Scavenging Enzymes during Extracorporeal Membrane Oxygenation in a Lamb Model

Abstract

We studied levels of superoxide dismutase, glutathione, reductase, glutathione peroxidase and lipoperoxides in 12 healthy lambs below 1 year of age (8-19 kg) under therapy with extracorporeal membrane oxygenation (ECMO). Plasma levels of these free oxygen radical scavenging enzymes and lipoperoxides were taken 1 day before the ECMO experiment, at the beginning of ECMO after the first rotations of the roler pump, during, and after ECMO. The pre-ECMO results of days 1 and 2 were compared with the during-ECMO results and those with the post-ECMO results using the t test for paired samples. We found a significant decrease of both superoxide dismutase and glutathione reductase on ECMO, a trend to increased lipoperoxide levels, and unchanged levels of glutathione peroxidase. After discontinuing bypass the levels began to normalize again. We conclude that ECMO reduces some oxygen radical scavenging enzyme levels and exhibits a trend to increased lipoperoxide levels. Near total lung collapse with consecutive reperfusion injury might be harmful considering these results. However, the nonsignificant increase in lipoperoxide levels excludes considerable oxygen toxicity during this short ECMO trial.

The impact of acute lung injury, ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model

“…When conventional medicine fails in these patients, ECMO is one of the few remaining life-saving options [4]. Previous ECMO studies in paediatrics [25], rabbits [26], lambs [27], sheep [28] and pigs [29] have shown significant elevations in lipid peroxides. However it is difficult to translate these findings to critically ill adult patients as (i) paediatric patients have significantly different bodyweight to ECMO surface area ratios and (ii) (with the exception of the sheep study [28]) in all the other animal models ECMO was initiated in a healthy host.…”

Selenium and oxidative stress modulation during extracorporeal circulation

“…67 However, in a lamb model of short duration ECMO, no increases in lipid peroxides were detected, instead there were decreases in the antioxidant enzymes SOD and GPx. 68 In the only clinical study investigating oxidative changes during ECMO, Hirthler et al showed increases in lipid peroxides for up to 96 hrs after initiation of ECMO in a paediatric population. 69 In this study non-survivors had increasing lipid peroxidation levels, while the levels plateaued after 24 hours in the survivor group.…”

“…67 Yet in contrast, investigators were unable to demonstrate significant increases in lipid peroxidation, despite high PaO 2 levels, in a healthy lamb model. 68 In a healthy porcine model of VV-ECMO, it was recently been demonstrated that significant increases in lipid peroxidation levels occur (as measured by MDA) as well as concurrent decreases in SOD activity. 149 The only animal study to investigate oxidative stress in a clinically relevant model of organ injury was conducted more than 30 years ago.…”

“…While limited animal studies have demonstrated an increase in oxidative stress when ECMO is used in healthy animals, [67][68][69]150 many of these studies have used ECMO circuits that are no longer available, thus questioning the relevance of the "old" published data to today's practice. Additionally, given that low selenium levels in the critically ill patient, independent of oxidative stress, are associated with adverse outcomes, 128 it is plausible that ECMO might also be associated with significant reductions in selenium and thus contribute to ECMO related complications and adverse outcomes.…”

“…A small number of animal studies were conducted in the late 1990's and documented increases in lipid peroxidation; however, these studies utilized circuits that had little clinical relevance to the modern ECMO circuit. 67,68,150 A clinical study investigated oxidative stress in paediatric patients on ECMO and also noted increases in lipid peroxides, but that study was also conducted in 1990 and also is of little clinical relevance to modern ECMO. 69 In 2014 a porcine study demonstrated significant increases in lipid peroxides in blood and tissue after initiating ECMO using current modern circuits.…”