Ischemic Preconditioning: From Basic Mechanism to Clinical Application

pp 285-299

Abstract

When the heart is subjected to a transient non-lethal period of ischemia, it quickly adapts itself to become resistant to infarction from a subsequent ischemic insult. This adaptation is called preconditioning (PC). This cardioprotection has been shown to be mediated by stimulation of receptors linked to PKC (adenosine, bradykinin, opioids, etc.)and these receptors protect by activating proteinkinase C (PKC). PKC appears to be the first element of a complex kinase cascade that is activated during the prolonged ischemia in the preconditioned heart. Recent studies imply that p38 mitogen-activated protein kinase (p38 MAPK) carries the signal from PKC to the mitochondrial K_ATP channels causing them to open and thus protect the heart.The cardioprotection of PC occurs in all species tested to date, and possibly also man. It is expected that as the mechanism of preconditioning is more thoroughly understood pharmacological preconditioning will become practical for clinical use.