Abstract

Purpose Mortality in adult patients requiring ECMO support is high. We aimed to identify biomarkers and potential pathophysiological mechanisms triggered by ECMO that could be responsible for adverse outcome. Oxidative stress during ECMO is increased and unbalanced oxidative stress is linked to the proteolytic cleavage of prolactin into an N-terminal 16kDa fragment with strong antiangiogenic and pro-apoptotic features. We hypothesize that prolactin and its cleavage products play a role in the pathopysiology of ECMO-related mortality. Methods and Materials Analysis of the kinetics of serum markers related to cardiac function, inflammation and prolactin in patients (n=47) before ECMO implantation, on defined time points during ECMOsupport and after ECMO explantation. Patients undergoing cardiac surgery (n=20) and healthy people (n=10) served as controls. Results were compared to kinetics of prolactin levels of patients requiring LVAD-implantation (n=5), after cardiac resuscitation (n=10), during sepsis (n=5) and patients with longterm LVAD-support with either stable (n= 25) or complicated (n=10) clinical course. Results Baseline prolactin levels were similar between ECMO-patients and control groups. Prolactin levels increased markedly after connection to ECMO, (from a mean of 20μg/l to a mean of 42μg/l in 24h), further increased during ECMO support (up to 174μg/l) and decreased after weaning from ECMO. Patients who died while being connected to ECMO or after weaning, developed prolactin levels which were significantly higher (mean 73μg/l ± 48 μg/l) compared to ECMO patients who survived (mean 28μg/l, ± 11 μg/l, p Conclusions Elevated prolactin levels are associated with a poor outcome in patients receiving ECMO-support, suggesting that prolactin could be used for risk stratification in these patients. In addition, with the potential adverse effect of 16kD prolactin on the endothelium, it may also be involved in the pathophysiology of ECMO-related mortality.

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