Murry et al found episodes of sublethal ischemia in dog protected the heart and reduced the infarct size caused by a subsequent more sustained period of coronary artery occlusion in l986. Since than,the phenomenon of brief antecedent ischemia to limit infarct size has been described in various experimental model and species. In addition a great of indirect evidence suggests that brief ischemia may also protect the human heart: the improved in-hospital outcome recen11y described in patients experiencing angina be fore myocardial infarction may represent a c1inical correlate with ischemic preconditioning. The mechanisms responsible for this protection remain unresolved, but experimental studies have demonstrated that the mechanisms of ischemic preconditioning does not involve opening collateral vesseis. Rather, brief ischmia seems to trigger an as yet unidentified endogenous subcellular adaptive response which acutely increases the tolerance of the myocytes to a subsequent ischemic insult. Recent experimental studies have extensively shown that endogenous adenosine released and catecholamine released during brief period of ischemia would be responsible initiators and mediators in protective ischemic preconditioning,but the opening of ATP-sensitive K+ channel and the activation of proteein kinase C might play a role of effector in protective ischemic preconditioning. Ultimately, it is hoped that exploiting this knowledge to develop preconditioningmimetics"to protect the human heart.
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