Ischemia reperfusion injury (IRI)

Ischemia reperfusion injury (IRI) is a reaction that breaks the self/non-self-barrier in medical conditions and treatment. When the intravascular innate immune system (IIIS) comes in contact with cells that have been affected by hypoxia, the cell surface is identified as foreign, which activates IIIS and causes a thromboinflammatory reaction. This reaction is the underlying cause of the injury and cell death that occurs when ischemic cells come in contact with blood.

reperfusion injury by transplantation

IRI appears during reperfusion of a transplanted organ. When the organ (e.g. kidney, liver, heart) is removed from the donor in connection to an individual being declared brain dead, it is stored at +4°C under ischemic conditions, which not only damages the organ by the ischemia including the endothelium so that the protection against IIIS-attacks in the vascular tree is destroyed. This protection is associated with the glycocalyx (GC) that coats the endothelial cells.

The GC protection is partly mechanical but is related to the GC-bound regulators of IIIS-components, e.g. ATIII, C1INH, factor H, C4BP. Due to ischemia, the GC of the cells is fragmented, leading to that the protection against the IIIS is lost. When the organ is reperfused with blood in connection with the transplantation, IRI injury is triggered, which among other side effects leads a delayed function of the organ. Delayed graft function is a prognostically bad sign for the organ’s long-term viability.