Increased inflammatory response and neovascularization in reperfused vs. nonreperfused murine myocardial infarction

Abstract

Introduction Fundamental knowledge of the inflammatory response after myocardial infarction (MI) is indispensable for intervention toward cardiac regeneration. Although reperfusion is preferred as clinical therapy, for basic research, also permanent ligation MI models are widely used. Methods In this report, we pathohistologically compared the kinetics of the inflammatory and angiogenic response after MI induced by permanent ligation or ligation followed by reperfusion of the left anterior descending coronary artery in mice. Results Permanent ligation resulted in a higher mortality rate accompanied by increased left ventricular dilatation and more progressive wall thinning. However, reperfused infarcts showed higher inflammatory cell influx. Neutrophil numbers were higher after reperfusion post-MI, although their presence was prolonged after ligation. Also, the number of macrophages after reperfusion was continuously higher, but the course of macrophage influx was comparable in both models. The number of lymphocytes was low in both models. Only the peak in myofibroblast numbers at 7 days was higher after ligation than after reperfusion. Moreover, cardiomyocyte remnants were cleared faster, and collagen deposition started earlier after reperfusion. In addition, reperfusion resulted in an increased angiogenic response, as was reflected in increased numbers of medium-sized and large vessels at 7 and 14 days post-MI. Conclusion We show less adverse remodeling together with a higher presence of inflammatory cells and enhanced neovascularization in reperfused MI. These differences between nonreperfused and reperfused MI should be taken into consideration for experimental use of MI models.