Postconditioning

Postconditioning, or ischemic postconditioning, is a protective strategy applied after a sustained ischemic event. It involves brief, intermittent episodes of ischemia during the early reperfusion period with the aim of reducing tissue injury, limiting infarct size, and improving functional recovery. The approach is distinct from ischemic preconditioning, which is applied before the ischemic insult.

The concept emerged from experimental studies in the early 2000s, particularly in cardiac models, where brief cycles of restored and re-occluded blood flow at the onset of reperfusion were shown to lessen tissue damage. Since then, postconditioning has been investigated in other organs, including the brain and kidneys, and in various species. It has also been explored as a variant of remote ischemic conditioning, where protective signals are triggered in a distant tissue.

Mechanistically, postconditioning is thought to engage pro-survival signaling pathways, such as the reperfusion injury salvage kinase (RISK) pathway and the SAFE (survivor activating factor enhancement) pathway. These signals can modulate mitochondrial responses, notably delaying or preventing the opening of the mitochondrial permeability transition pore, reducing reactive oxygen species production, and dampening inflammatory processes. Collectively, these effects help preserve mitochondrial function and cellular viability during the critical reperfusion period.

Clinical translation has yielded mixed results. In patients with acute myocardial infarction undergoing reperfusion therapy, some trials have reported reduced infarct size or improved outcomes, while others have found no significant benefit. Ongoing research seeks to define optimal protocols, timing, and patient selection, as well as to evaluate pharmacological postconditioning strategies that mimic the protective signals without mechanical ischemia cycles.