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Ischemic preconditioning

Ischemic preconditioning
MeSH D019194
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Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of ischaemia protect the against a subsequent ischaemic insult. It was first identified in 1986 by Murry et al. This group exposed anesthetised open-chest dogs to four periods of 5 minute coronary artery occlusions followed by a 5-minute period of reperfusion before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of “ischaemic preconditioning” and had much larger infarct sizes compared with the dogs that did. The exact molecular pathways behind this phenomenon have yet to be fully understood.

If the blood supply to an organ or a tissue is impaired for a short time (usually less than five minutes) then restored so that blood flow is resumed, and the process repeated two or more times, the cells downstream of the tissue or organ are robustly protected from a final ischemic insult when the blood supply is cut off entirely and permanently.

The protective effect which is imparted by IPC has two windows of protection. The first, lasts between 4–6 hours and has been named classical or early preconditioning. The second window begins at 24 hours lasting up to 72 hours post the ischaemia and reperfusion stimulus.

In an experimental setting if the left anterior descending coronary artery of the animal is ligated the downstream cardiac cellular mass is infarcted and will be injured and then die. If, on the other hand the tissue is subjected to IPC the downstream cellular mass will sustain only minimal to modest damage. IPC protects the tissue by initiating a cascade of biochemical events that allows for an up-regulation of the energetics of the tissue. The locus of this phenomenon is the intracellular organelle, the .

Investigations of various exogenous circulating ligands such as the delta active opiates and opioids simulate the phenomenon of IPC thus protecting the downstream tissues without the IPC intermittent ligating procedure.


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