Unraveling the mysteries of classical preconditioning

Nearly two decades have passed since the first report about ischemic preconditioning. Although we do not yet know unequivocally what the final effector is, we have learned a lot about the signal transduction pathways that result in protection, and have some good prospects for the final step that results in survival or necrosis of the ischemic myocardium. Many investigators have contributed to our current knowledge. We were heartened to learn that four of our JMCC publications are included in the 20 top-cited papers in the journal's history. It is gratifying that our prior publications have generated some interest and stimulated important debate as documented by the high number of citations by scientists in the bibliographies of their own papers. In this document, we have been asked to reflect on those four papers and comment on where they have led us.