Signal transduction in ischemic preconditioning.

Ischemic preconditioning is a phenomenon in which exposure of the heart to a brief period of ischemia causes it to quickly adapt itself to become resistant to infarction from a subsequent ischemic insult. The mechanism is not fully understood but, at least in the rabbit, it is known to be triggered by occupation of adenosine receptors, opioid receptors, bradykinin receptors and the generation of free radicals during the preconditioning ischemia. All of these are thought to converge on and activate protein kinase C (PKC), which in turn activates a tyrosine kinase. This kinase cascade eventually terminates on some unknown effector, possibly a potassium channel or a cytoskeletal protein, which makes the cells resistant to infarction. If this process can be understood, it should be possible to devise a method for conferring this protection to patients with acute myocardial infarction.