Reperfusion Injury After Hemorrhage: A Collective Review

G D. Rushing, MD; L D. Britt, MD, MPH


Annals of Surgery. 2008;247(6):929-937. 

In This Article

Endothelium, Its Role in Reperfusion Injury

Reperfusion injury starts with the simple reoxygenation of tissues after ischemic insult causes hypoxia. Regardless of the cause of hypoxia, endothelium seems to be the primary starting ground for reperfusion injury. Endothelial cells are known to be sensitive to hypoxia, manifesting damage via an increase in cellular volumes, loss of cytoskeletal organization, and decreased membrane fluidity. Energy stores are depleted and certain bioactive agents including prostacyclin and nitric oxide (NO) are used to maintain anticoagulation.[44] Early in reperfusion, endothelial cells exhibit morphologic damage including cellular swelling, loss of adherence to the basement membrane, and adherence of activated leukocytes.[45]

The location of endothelial damage is found throughout the vascular system specifically at the level of arterioles, capillaries, and venules. The postcapillary venule is the most common site of inflammatory response due to reperfusion.[46] Injury is heralded by several venule responses after ischemia, which includes the following: leukocyte-endothelial cell adhesion, transendothelial migration, platelet-leukocyte aggregation, and enhanced oxidant production. Intravital microscopy has been a key tool in verification of endothelial damage occurring in venules during reperfusion after ischemia. Several studies have shown endothelial leakage using fluorescein isothiocyanate conjugated albumin as a marker.[47,48,49] This leaky vasculature has been linked to adhesion of leukocytes as well. It seems that the volume of adherent leukocytes is directly correlated with the amount of extravasated albumin.[50]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.