The science and clinical translation of remote postconditioning.

The treatment of reperfusion injury requires measures beyond timely reperfusion. Conventional postconditioning (PostC) of ischemic tissues offers a strategy to reduce reperfusion injury, but its adoption is challenged by requiring access and imposing additional ischemia to the ischemic organ. Generating protective signals by PostC in a tissue remote from the target organ such as the limb, i.e. remote PostC (rPostC), may present an alternative approach to exerting endogenous tissue protection. Because rPostC is only recently reported, the fundamental biology of rPostC is not well understood, and studies to date are largely observational. rPostC has been observed to reduce ischemia-reperfusion injury experimentally in heart, kidney, brain and skeletal muscle in multiple species, including rat, rabbit and pig. Both necrosis and apoptosis are reduced. As in remote ischemic preconditioning, rPostC requires a transfer or communication of protective factors or signals through humoral and/or neural pathways. Triggers of target organ protection include G-protein-coupled receptor ligands, metabolites of ischemia, or small thermolabile molecules. Some evidence suggests that reperfusion injury salvage kinases may be involved in rPostC, in agreement with both preconditioning and conventional PostC. Clinical studies investigating improvements in clinical outcomes or biomarkers with rPostC are encouraging.