Time to Give Up on Cardioprotection?

Both the incidence of acute ST-segment–elevation myocardial infarction (STEMI) and the mortality from STEMI have decreased over the last 3 decades. However, despite the success of reperfusion therapy by primary percutaneous coronary intervention (PCI) or thrombolysis, STEMI is still of significant concern. Although door-to-balloon time for primary PCI has declined, mortality has not, possibly because of an increasing number of older and sicker patients. Also, patients who survive an acute myocardial infarction (AMI) often develop heart failure, and the prevalence of heart failure is increasing in developed countries. Infarct size is the major determinant of patients’ outcome. Clearly, timely and complete reperfusion is the most effective way to limit infarct size. However, reperfusion also adds an additional reperfusion injury on top of ischemic injury, and it, thus, contributes to infarct size. Therefore, additional interventions and treatments on top of timely reperfusion are still needed to reduce infarct size and improve the clinical outcome of patients with AMI. Apart from acute STEMI (type 1 myocardial infarction), additional cardioprotection is also sought in elective PCI with the aim to reduce periprocedural myocardial infarction (type 4a) and in surgical coronary revascularization with the aim to reduce perioperative myocardial infarction (type 5); in some studies, cardioprotection was also sought in major cardiovascular surgery other than coronary artery bypass grafting (CABG). In the animal experiment, the conditioning phenomena are the most powerful cardioprotective, that is, infarct size reducing interventions. Ischemic preconditioning describes brief episodes of myocardial ischemia/reperfusion before the sustained coronary occlusion that results in infarction. Ischemic postconditioning describes brief episodes of coronary reocclusion/reperfusion in the immediate reperfusion phase after a sustained coronary occlusion that results in infarction. Remote ischemic conditioning describes brief episodes of ischemia/reperfusion of an organ or tissue remote from the heart; these episodes of distant ischemia/reperfusion can precede (preconditioning), follow (postconditioning), or occur in parallel (perconditioning) to the sustained coronary occlusion that causes the infarction. The most Review