Pre-emptive conditioning of the ischemic heart

Ischemic heart disease remains one of the most frequent causes of morbidity and mortality worldwide. Although the prognosis of myocardial ischemia has been dramatically improved by the techniques of early reperfusion, the prevention of irreversible ischemic damage remains a critical aspect of the treatment. An appealing novel therapeutic avenue for the prevention of myocardial ischemia relates to the possibility of a pre-emptive conditioning of the heart, in which an activation of survival pathways could be achieved in patients with ischemic heart disease who are at risk for a subsequent lethal ischemia. These patients would include those with unstable angina, or with severe and repetitive ischemic episodes, and patients scheduled for surgical revascularization. In these situations, the pre-emptive activation of survival signaling mechanisms would confer a prophylactic cardioprotection during the following ischemic stress. During the last twenty years, it became clear that the heart can trigger survival mechanisms when submitted to stress, in such conditions as myocardial stunning, hibernation and preconditioning. The goal of the pre-emptive conditioning is to activate such survival pathways as a prophylactic measure to prevent myocardial cell death when the heart is threatened by potentially lethal ischemia. Based on the experimental data collected at the bench side, we review how this approach could be applied in the clinical setting.