Ischemic preconditioning

Ischemic preconditioning (IPC) is a hormetic phenomenon in which brief, sublethal cycles of tissue oxygen deprivation followed by reperfusion protect against a subsequent lethal ischemic event. Murry, Jennings, and Reimer (1986) showed four 5-minute coronary occlusions in dogs reduced infarct size by ~75%. Two protection windows operate: an early phase (1–3 h) driven by adenosine receptors, protein kinase C (PKC), and ATP-sensitive potassium channels (K_ATP); and a late phase (12–24 h) requiring de novo synthesis of heat-shock protein 70 and inducible nitric oxide synthase. Both converge on inhibition of the mitochondrial permeability transition pore (mPTP), preventing the membrane permeabilization that kills cardiomyocytes at reperfusion. Remote IPC (RIPC), induced by limb cuff inflation, transmits protection via humoral mediators (nitrite, SDF-1, micro-RNAs) and autonomic pathways. Aging blunts PKC signalling and K_ATP responsiveness — a deficit caloric restriction and exercise can partly reverse. Despite consistent animal data, two large randomised trials (ERICCA n≈1,600; RIPHeart n≈1,400; 2015) found no benefit after cardiac surgery under propofol, implicating anaesthetic interference. RIPC for stroke prevention or broader organ protection remains investigational.