An Overlooked Mechanism for Ischaemic Preconditioning?

Ischaemic preconditioning is a process whereby a period of partial ischaemia, short of a duration resulting in damage, can protect against a subsequent more severe ischaemic episode. The phenomenon was first reported by Murry et al. [1] who showed that short periods of coronary artery occlusion in dogs produced a degree of protection to the heart against more prolonged occlusion. Subsequently it was found that the protective initial ischaemia did not need to be produced in the tissue later exposed to the major ischaemic insult [2], but that cardioprotection, for example, could be effected by short periods of limb ischaemia using a simple blood pressure cuff around the arm. This is termed remote (or distal) ischaemic preconditioning and has become one of the most powerful interventions for reducing myocardial infarction size in ischaemic hearts [3], as, for example, in patients undergoing heart valve surgery. They noted however, as have many others, that incomplete comprehension of the mechanisms underlying the process could be impairing the design of clinical trials and the interpretation of their results.