Postconditioning During Primary Coronary Intervention: The Effects of on Elevation

To the Editor: We read with interest the article by Hahn et al evaluating the effect of mechanical postconditioning on the prevention of lethal reperfusion injury. In this study, angioplasty postconditioning failed to improve ST segment resolution. This large trial contrasts with previous results of animal studies or human small-sized trials suggesting a positive or a neutral effect of such a strategy on the reduction of infarct size. We draw attention to the following limitations that could have hampered the eventual beneficial effect of ischemic postconditioning. The main difference between animal models of myocardial infarction and human clinical settings relies on the importance of the thrombotic burden. Indeed, in most of the animal models, myocardial infarction was induced by coronary ligation. Given the low thrombotic burden, the risk that thrombus dislocation and residual microvascular obstruction might alleviate the beneficial impact of mechanical postconditioning is limited. By contrast, the high thrombotic load observed in patients with ST-segment–elevation myocardial infarction may contribute to microvascular obstruction when iterative balloon angioplasty was performed at the site of thrombus formation. Recent optical coherence tomography data have demonstrated the huge amount of the atherothrombotic burden that follows stent implantation, with a residual thrombus being detected in 100% of the cases. Not surprisingly, residual thrombotic burden was an important predictor of ST resolution failure. To avoid thrombus fragmentation, previous positive studies on mechanical postconditioning were used to perform iterative balloon angioplasty proximal to the culprit lesion in clear opposition with the present study where postconditioning was performed within the stent. Analyses from the postconditioning during coronary angioplasty in acute myocardial infarction trial have suggested that, when reinflation was made within the stent, this strategy could increase infarct size. Another concern refers to the very low rate of direct stenting reported in the study by Hahn et al1 (13.4%). Previous reports have suggested that the noxious effects of coronary microembolizations on ischemic postconditioning-induced cardioprotection might be blunt if direct stenting was used. The very low rate of complete ST resolution observed in the present study (41%) is consistent with the microembolization hypothesis that could have mitigated the protective effect of postconditioning. In our practice, ST segment resolution could be obtained in 65% to 70% of the cases, with direct stenting being performed in ≥46%. Another aspect worth considering when comparing pharmacologic versus ischemic mechanical postconditioning is their opposite impact on procoagulant microparticle (MP) release. In patients with ST-segment–elevation myocardial infarction, elevated concentration of MPs harboring tissue factor activity could be detected in the vicinity of the coronary thrombus. Such MPs are potent mediators of the no-reflow phenomenon, wherein when microembolization occurred, intracoronary levels of MPs were important predictors of ST resolution failure. Although ischemic postconditioning is associated with the release of endothelial and procoagulant MPs, experimental data have suggested that cyclosporine A may decrease procoagulant MP release. Therefore, in the context of huge thrombotic burden, we believe that pharmacologic modulation of lethal reperfusion injury by cyclosporine A acting not only on cardiomyocyte cell death but also on the release of MPs might be an attractive option. Hahn et al are to be commended for their careful assessment of mechanical postconditioning. Nevertheless, their findings clearly highlight the need to test other approaches to limit lethal reperfusion injuries.