Alternative pharmacological interventions that limit myocardial infarction

Despite current optimal treatment, the morbidity and mortality of coronary heart disease remain significant worldwide and open the way for the development of novel cardioprotective therapies. In the last two decades, a remarkable scientific effort has focused on the limitation of infarct size. Important input from experimental studies has led the way in this direction. However, clinical and preclinical results using various cardioprotective strategies to attenuate reperfusion injury have generally not been applicable for every day clinical practice. Protection of the ischemic myocardium is known to occur as a result of ischemic preconditioning (PC), in which repetitive brief periods of ischemia protect the heart from a subsequent prolong ischemic insult. Although PC is a powerful form of protection, it is of limited clinical application for obvious ethical and practical reasons. Another endogenous form of cardioprotection, similar to PC but applicable at the time of reperfusion, termed postconditioning (PostC), has been recently described. Short series of repetitive cycles of brief reperfusion and re-occlusion of the coronary artery applied at the onset of reperfusion, reduce the infarct size and coronary artery endothelial dysfunction. At present, pharmacological PC and PostC are possible alternative methods that may substitute pharmaceutical treatments the short ischemic insults. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. We summarize the recent research efforts on novel therapeutic strategies and on the design of new compounds, based on the accumulated knowledge of the ligands, receptors and intracellular signaling pathways of PC and PostC.