ABSTRACT
It has long been recognized that reduced delivery of oxygen to tissue results in cellular dysfunction, tissue injury, and subsequent cell death. Ischemia results in oxygen deprivation due to reduced blood flow caused by diseases such as myocardial infarction, stroke, or tumor; or it may be a by-product of a medical intervention such as tissue transplantation or surgery accompanied by hypoperfusion of one or more tissues. Based on the observation that the duration of oxygen deprivation correlates directly with the degree of cellular injury, it was thought that tissue injury resulted primarily from ischemia
per se
, and the primary aim of physicians throughout history has been to restore blood flow to the affected tissue as rapidly as possible. Although the restoration of blood flow to occluded large blood vessels, or reperfusion, is
necessary for the recovery of cell function, it is now known that restored blood flow is often accompanied by secondary injury that occurs as a result of inflammation during reperfusion, referred to as
reperfusion injury
or
ischemia-reperfusion injury
(IRI). Reperfusion injury results in part from the occlusion of microvessels with adherent platelets and leukocytes. The extent of injury that occurs as a consequence is partly due to the activation of endothelial adhesion molecules and the release of cytokines from tissue-resident inflammatory cells. Hence, IRI can be divided into an initial phase that occurs during ischemia and a secondary phase that occurs during reperfusion and is associated with inflammation.
