Guidelines for in vivo mouse models of myocardial infarction

Abstract

Despite significant improvements in reperfusion strategies, acute coronary syndromes all too often culminate in a myocardial infarction (MI). The consequent MI can, in turn, lead to remodeling of the left ventricle (LV), the development of LV dysfunction, and ultimately progression to heart failure (HF). Accordingly, an improved understanding of the underlying mechanisms of MI remodeling and progression to HF is necessary. One common approach to examine MI pathology is with murine models that recapitulate components of the clinical context of acute coronary syndrome and subsequent MI. We evaluated the different approaches used to produce MI in mouse models and identified opportunities to consolidate methods, recognizing that reperfused and nonreperfused MI yield different responses. The overall goal in compiling this consensus statement is to unify best practices regarding mouse MI models to improve interpretation and allow comparative examination across studies and laboratories. These guidelines will help to establish rigor and reproducibility and provide increased potential for clinical translation.

Keywords: cardiac; ischemia-reperfusion; myocardial infarction; rigor and reproducibility; rodent.

Figure 1.

Key differences between reperfused myocardial infarction (MI) and nonreperfused MI, including differences in infarct sizes, study goals, structural and physiological responses, survival, and cell and molecular signaling. For the reperfused heart, the mid-myocardial section was stained with Evans blue (in vivo) and 1% triphenyltetrazolium chloride (ex vivo) to show the necrotic zone (NEC; white), nonischemic zone (NIZ; blue), and ischemic zone (IZ; red and white) (41). For the nonreperfused heart, the ventricles were sectioned from base (left) to apex (right) and stained with 1% triphenyltetrazolium chloride, which stains viable myocardium red and infarct is white (42). Images are reproduced with permission from the American Journal of Physiology-Heart and Circulatory Physiology.