Microvascular dysfunction during extracorporeal circulation The role of hemolysis

Extracorporeal circulation, including extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), has become an essential life-saving therapy for patients with severe cardiac and/or respiratory failure. Despite its clinical benefits, these techniques are frequently accompanied by complications such as microvascular dysfunction and acute kidney injury (AKI). The mechanisms underlying these complications are not fully understood, but hemolysis has emerged as a potential contributing factor.
This thesis investigates the interplay between hemolysis, endothelial injury, and microvascular dysfunction during extracorporeal circulation, with a particular focus on the role of cell-free hemoglobin (CFHb). The clinical studies presented demonstrate that microvascular dysfunction may persist during ECMO and is characterized by sustained endothelial injury, while hemolysis follows a dynamic course over time. Although higher levels of hemolysis were observed in patients with worse outcomes, hemolysis alone did not independently predict AKI, emphasizing the multifactorial nature of organ injury.
To further explore underlying mechanisms, experimental animal and in vitro models were used. These studies show that ECMO itself induces hemolysis, endothelial injury, and impaired microcirculatory perfusion. In addition, CFHb was found to directly disrupt endothelial barrier function and reduce microvascular perfusion, supporting its role as a mediator of vascular dysfunction.
In summary, this thesis demonstrates that hemolysis, endothelial injury, and microvascular dysfunction are closely interconnected and play a central role in renal injury during extracorporeal circulation, and provides a foundation for future research aimed at improving patient outcomes.