)The therapeutic strategies for acute myocardial infarction in the last decade have, among other therapeutic targets, focused on myocardial reperfusion injury, which accounts for a significant part of the final infarct size. Although several experiments in the last 20 years have reported that pharmacological interventions at reperfusion might reduce myocardial reperfusion injury, this could not be consistently confirmed in animal models or human studies. An alternative to chemical modifiers, postconditioning (brief repeated periods of ischemia applied at the onset of reperfusion) is the first method proven to be efficient in different animal models and to be confirmed in a recent human study. This simple method, applied in the first minute of reperfusion, reduces the final infarct size by 30-50%. This review will focus on the postconditioning technique and show how the data from different animal models and experimental settings have advanced our understanding of both the mechanisms and the definition of an accurate protocol that is easily applicable in human patients in the setting of acute myocardial infarction.
Disease Models & Mechanisms DMMlonger ischemic insult on experimental models (Murry et al., 1986), the idea of mechanical postconditioning emerged as a potential therapeutic strategy applicable to AMI patients. The initial, experimental proof-of-concept study was developed by Zhao et al. on an ischemia-reperfusion model of open-chest dogs (Zhao et al., 2003). In this first experiment, after 60 minutes of left anterior descending coronary artery (LAD) occlusion, reperfusion was initiated for 30 seconds followed by 30 seconds of reocclusion, which was repeated for three cycles (i.e. the total intervention lasted for 3 minutes). Reperfusion was continued for a total of 3 hours in all experiments. The results of this study showed that the infarct size in the postconditioning group was 44% smaller than that in the control group and that there was no statistical difference in infarct size between the preconditioning and postconditioning groups (Fig. 1).In this same experimental study, the authors found that postconditioning was associated with a significant reduction of myocardial edema at the myocardial area at risk. Postconditioning reduced the accumulation of polymorphonuclear neutrophils (PMNs) in the same area and attenuated PMN adherence to the endothelium by reducing P-selectin expression on coronary vascular endothelium. Postconditioning also significantly reduced the lipid peroxidation in the myocardial area at risk compared with the control group. All those results showed that postconditioning significantly reduced the reperfusion injury phenomenon.This observation has since been confirmed in several experimental preparations and with different animal species (rats, rabbits and mice), showing that, when applied at the time of reperfusion, postconditioning significantly reduced infarct size with results comparable to preconditioning (Bopassa et al., 2006;Bopassa et al., 2005; Kin et al., 2005; Kin et...