| Cross |
Preconditioning stimulus is different from the noxious stimulus against which it protects |
In the earliest description of the technique20 the same stimulus was used to induce preconditioning and damage (trauma), whereas trauma was used by Janoff 21to induce protection against sterile sepsis and bowel ischaemia |
| Remote |
Preconditioning of one organ or system leads to protection of a different (remote) organ |
The prototypical approach for remote preconditioning is the initiation of short ischaemic intervals to a limb to protect organs such as the heart22,23 and brain.24-26 Remote preconditioning might indicate a crosstalk between the brain and the rest of the body in response to stress. Randomised clinical trials have already shown the efficacy of this strategy for the heart.27,28 Remote preconditioning is a particularly attractive strategy to protect organs that are highly susceptible to damage but that are difficult to target, such as the brain |
| Immunological |
Pharmacological compounds that trigger the signalling cascades of preconditioning (without a physical stimulus) |
One of the earliest examples of pharmacological preconditioning was the mild inhibition of the respiratory chain with nitropropionic acid or acetylsalicylic acid,35-38 which induced cellular changes such as those seen with hypoxia. Another relevant example is the use of the iron chelator desferrioxamine,39 which induces nuclear translocation of the transcription factor hypoxia-inducible factor 1, with consequent expression of a plethora of hypoxia-inducible genes, including erythropoietin, vascular endothelial growth factor, and hexokinase |
| Anaesthetic |
Short application of any one of many different classes of anaesthetics can induce an ischaemia-protected state |
Anaesthetic preconditioning is effective in the heart40,41 and brain.42-45 This protection might happen within minutes or might be delayed by many hours or days. For practical reasons, anaesthetic preconditioning is an appealing therapeutic option that has already been tested in randomised controlled trials for cardiac protection |
| Mimetics |
Compounds that emulate the main danger signal can lead to preconditioning |
Examples include inhibitors of mitochondrial respiration, stabilisers of hypoxia-inducible factor 1 (signal: hypoxia), or lipopolysaccharide (signal: infection)46,47
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| Effectors |
The downstream mediators of protection |
These effectors include proteins such as erythropoietin, vascular endothelial growth factor, and BCL family proteins. These proteins are attractive pharmacological candidates for preventing the consequences of anticipated ischaemia |
