Remote ischemic preconditioning: current knowledge, unresolved questions, and future priorities.

Remote ischemic preconditioning (RIPC) is the phenomenon whereby brief episodes of ischemia-reperfusion applied in distant tissues or organs render the myocardium resistant to a subsequent sustained episode of ischemia. Reduction of infarct size with RIPC has been documented in response to (i) brief antecedent ischemia in a remote coronary vascular bed (intra-cardiac protection); (ii) collection and transfer of coronary effluent from perconditioning "donor" hearts to naive "receptor" hearts (inter-cardiac protection); (iii) brief ischemia applied in skeletal muscle, mesentery, and other organs (interorgan protection); and (iv) remote nociception ("remote PC of trauma"). Moreover, the paradigm has expanded to encompass temporal modifications in the application of the remote stimulus (remote perconditioning and remote postconditioning). Progress has also been made in translating the concept of RIPC to patients undergoing planned ischemic events: evidence for attenuation of cardiac enzyme release with RIPC has been reported after elective abdominal aortic aneurysm repair, angioplasty, and coronary artery bypass graft surgery. However, despite these advances in characterization and clinical application, the mechanisms of RIPC--most notably, the means by which the protective stimulus is communicated to the heart--remain poorly defined and, in all likelihood, are model dependent.