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1 Experimental Cardiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
2 Cell Biology and Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Vascular Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: e.vandenbos{at}erasmusmc.nl.
Mouse myocardial infarction (MI) models are frequently used research tools. The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 weeks. Cryoinfarction was induced using a 2 or 3 mm cryoprobe. 2D guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and endpoint. At endpoint, hemodynamics were assessed using a 1.4F Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histologic and morphometric analysis of infarct and remote areas was performed. At 4 weeks, 3 mm cryoinfarction resulted in decreased LV fractional shortening, as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 weeks after cryoinfarction with further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone shaped infarcts with reperfusion at a macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice.
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