Delayed preconditioning of the human myocardium: signal transduction and clinical implications.

OBJECTIVE Ischemic preconditioning confers cardioprotection in early and delayed phases. We investigated the delayed window of pharmacological and ischemic preconditioning in human myocardium, and the involvement of mitoKATP, PKC and p38MAPK. METHODS These studies were carried out using human right atrial tissue in a cell necrosis model. The tissue was obtained from patients undergoing coronary artery surgery. RESULTS The second window triggered by ischemia, phenylephrine or adenosine resulted in similar cardioprotection between 24 and 72 h following the intervention. Atrial tissue taken from patients with a single episode of angina between 24 and 72 h prior to surgery were already protected and preconditioning with ischemia, phenylephrine or adenosine did not add to the protection. The trigger of preconditioning with mitoKATP channel opener diazoxide, PKC activator PMA and p38MAPK activator anisomycin produced similar delayed protection to that of ischemia or phenylephrine. Cardioprotection was lost when mitoKATP channels were blocked by 5HD, PKC by chelerythrine and p38MAPK by SB203580 24 h after the trigger of preconditioning. CONCLUSIONS Ischemic and pharmacological preconditioning induce similar delayed cardioprotection of the human heart. This second window of protection that is seen between 24 and 72 h occurs in vitro and in vivo and requires opening of mitoKATP channels and activation of PKC and p38MAPK.