Metodología innovadora para el estudio del efecto que ejerce el daño por isquemia-reperfusión sobre la obstrucción microvascular en muestras de miocardio de un modelo in vivo de infarto de miocardio

Abstract

Background. Microvascular obstruction (MVO) exerts deleterious effects after myocardial infarction (MI). We aimed to describe a new methodology to accurately evaluate MVO in an in vivo model and to elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of this process. Methods. MI was induced in swine by means of 90-min occlusion of the mid left anterior descending coronary artery (LAD) using angioplasty balloons. Intra-coronary infusion of Thioflavin-S (T-S) was applied and compared with traditional intra-aortic or intra-ventricular instillation. LAD-perfused area (stained with T-S) and MVO (% of LADperfused area with a lack of T-S staining) were quantified in groups with no reperfusion (T-S administered distally through the lumen of an inflated over-the-wire balloon) and with 1-min, 1-week and 1-month reperfusion (T-S administered proximally from the intra-coronary catheter after balloon deflation). Results. In comparison with intra-aortic and intra-ventricular administration, intracoronary infusion of T-S permitted a much clearer assessment of LAD-perfused area and of MVO. Ischemia-reperfusion injury exerted a decisive role on the occurrence and dynamics of MVO. The no reperfusion group displayed completely preserved perfusion. With the same duration of coronary occlusion, MVO was already detected in the 1-min reperfusion group (14±7%), peaked in the 1-week reperfusion group (21±7%) and significantly decreased in the 1-month reperfusion group (4±3%, p<0.001). Conclusions. The described porcine model using intra-coronary injection of T-S permits an accurate characterization of MVO after MI. We present proof-of-concept evidence on the crucial role of ischemia-reperfusion injury on the occurrence and dynamics of MVO.