Activation of Ecto-5′-nucleotidase and cardioprotection by ischemic preconditioning

Since Jennings and his colleagues found that preceding brief periods of myocardial ischemia limit infarct size following sustained ischemia and reperfusion (11), termed as “ischemic preconditioning”, many basic and clinical researchers have focused on the cellular mechanisms of this potent cardioprotection. Downey and his colleagues (10) observed that 8-sulfophenyltheophylline blunts the infarct size-limiting effect of ischemic preconditioning in the rabbit heart. This evidence may point to two hypotheses: 1) adenosine makes the myocardium resistant against the lethal ischemic injury (adenosine as a trigger substance), and 2) ischemic preconditioning makes adenosine act more effectively during the lethal ischemic insult (adenosine as a mediator substance). Since adenosine is known to have many different beneficial cardiovascular effects against ischemia and reperfusion injury (1, 3), we hypothesized the latter mechanism as a candidate of the cellular mechanism of ischemic preconditioning.