Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size in Post-PCI Patients

ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI). In the animal model, a sharp drop in circulating T lymphocytes occurred within the first hours after reperfusion. Notably, increased apoptosis of circulating lymphocytes and infiltration of proinflammatory Th1 lymphocytes in the heart were observed 48 h after reperfusion. Similarly, in STEMI patients, a sharp drop in circulating T lymphocyte subsets occurred within the first 24 h post-PCI. A cardiac magnetic resonance (CMR) evaluation of these patients revealed an inverse association between 24 h circulating T lymphocyte numbers and infarction size at 1-week and 6-month post-PCI. Our translational approach revealed striking changes in the circulating and tissue-infiltrating T lymphocyte repertoire in response to ischemia-reperfusion. These findings may help in developing new diagnostic and therapeutic approaches for coronary diseases

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine

Background: Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model. Methods: A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angio-plasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an angioplasty balloon-induced anterior STEMI model, MVO was defined as the % of area at risk without thioflavin-S staining. Results: In patients, PCON (n = 49) in comparison with non-PCON (n = 52) did not significantly reduce MVO (0 [0-1.02]% vs. 0 [0-2.1]% p = 0.2) or IS (18 +/- 13% vs. 21 +/- 14%, p = 0.2). MVO (>1 segment in the 17-segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients, p = 0.3. No significant differences were observed between PCON and non-PCON patients in left ventricular volumes, ejection fraction or the extent of hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%) non-PCON pigs, p = 0.9. The extent of MVO (10 +/- 7% vs. 10 +/- 8%, p = 0.9) and infarct size (23 +/- 14% vs. 24 +/- 10%, p = 0.8) was not reduced in PCON compared with non-PCON pigs. Conclusions: Ischemic postconditioning does not significantly reduce microvascular obstruction in ST-segment elevation myocardial infarction.The present study was supported by the "Instituto de Salud Carlos III" (PI1102323 grant), FEDER, the "Conselleria de Educacio, Cultura i Esport de la Generalitat Valenciana" (PROMETEO/2013/007 grant) and by the Regensburger Forschungsforderung in der Medizin (ReForM).Bodí, V.; Ruiz Nodar, JM.; Feliu, E.; Minana, G.; Nuñez, J.; Husser, O.; Martinez Elvira, J.... (2014). Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine. International Journal of Cardiology. 175(1):138-146. https://doi.org/10.1016/j.ijcard.2014.05.003S138146175