Figure 6.2.

Total injury sustained by a tissue subjected to prolonged ischemia followed by reperfusion (I/R) is attributable to an ischemic component and a component that is due to reestablishing the blood supply. At the onset of prolonged ischemia two separate pathologic processes are initiated. The first are processes of tissue injury that are due to ischemia per se. The second are biochemical changes during ischemia that contribute to the surge in generation of reactive oxygen species and infiltration of proinflammatory neutrophils when molecular oxygen is reintroduced to the tissues during reperfusion particularly the initial phases. For a treatment to be effective when administered at the onset of reperfusion, reestablishing the blood supply must occur before damage attributable to ischemia per se represents a major component of total tissue injury. Therapeutic approaches that target pathologic events contributing to both the ischemic and reperfusion components of total tissue injury, such as ischemic or pharmacologic preconditioning, should be more effective than therapies administered when the blood supply is re-established, which limit only the progression of reperfusion injury. Modified from Bulkley (1987).