The difference in kinetic profile is intriguing and warrants further investigation.The negative correlation between plasma TRX levels and arterial pO2 at admission that we found in our study advocates against a role of hyperoxia in the onset of oxidative stress. There is a great controversy surrounding hyperoxia after CA resuscitation, www.selleckchem.com/products/baricitinib-ly3009104.html with some experimental data suggesting that hyperoxia might increase oxidative stress. While animal models were inconclusive [36], a human study suggested that hyperoxia was independently associated with in-hospital mortality, as compared with hypoxemia or normoxia [37]. However, the latter finding was refuted by both a study, in which this association did not appear in a large cohort, with adjustment on severity scores [36] and also our findings in the current work.

Nevertheless, further studies are required to elucidate this hot topic [38,39].TRX reflects both inflammation and oxidative stress, two major determinants of severity of post-cardiac arrest syndrome and could be considered as a potential marker of the global insult. However, the clinical utility of TRX has to be further established [40], as does the mechanistic explanation linking increased TRX levels with the biological disorders occurring after CA and post-cardiac arrest syndrome. TRX is elevated on admission, whereas vasoplegia and myocardial dysfunction typically begin a few hours after CA. In the future, utilizing biomarkers of inflammation and oxidative stress might allow tailoring therapeutic interventions that modulate inflammation or oxidative stress such as high volume hemofiltration [41] or steroids administration [42].

Besides its role of biomarker, TRX could be a future therapeutic target. Hofer et al. demonstrated, in an experimental model of cecal ligature and puncture, that neutralization of endogenous TRX was deleterious for septic mice survival, whereas treatment with recombinant TRX markedly enhanced their survival [14]. To date, no human data of such protective effects of TRX is available. However, major hope arose in the field of resuscitation after the use of coenzyme Q10, a mitochondrial enzyme playing a key role in antioxidant defense. In 49 Carfilzomib patients experiencing CA, exogenous administration of this antioxidant improved both survival and neurological outcome [43]. Further investigations are required to determine the place of TRX modulation in the armamentarium of critical care therapeutics.Although these data suggest that TRX could reflect a response to inflammation and oxidative stress, the functional consequences of high levels of TRX are not completely understood.