Endothelial activation by liver reperfusion injury

Endothelial Activation by Liver Reperfusion Injury in Transplantation Ischemia-reperfusion injury during liver transplantation is a profound inflammatory phenomenon that injures remote organs and worsens patient outcomes. The rising global need for liver transplantation has increased the use of marginal quality grafts, such as those with steatosis or from donors after cardiac death. Coagulopathy and acute kidney injury often arise after reperfusion of marginal grafts. These observations suggest a mechanism of pathologic endothelial activation downstream of liver reperfusion. We have hypothesized that liver ischemia-reperfusion releases endogenous Toll-like receptor agonists into the circulation, triggering diffuse endothelial activation and dysfunction. In this translational research, human serum collected from liver transplant patients at baseline and following reperfusion of the liver graft is applied to cultured endothelial cells. Transendothelial resistance is measured to quantify endothelial barrier function and permeability changes. This work aims to elucidate mechanisms by which inflammation and ischemia-reperfusion injury drive endothelial activation, which is of broad relevance to the fields of anesthesia and critical care in addition to liver transplantation.