A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1291-300. doi: 10.1152/ajpheart.00111.2005. Epub 2005 Apr 29.

Abstract

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 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 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 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone-shaped infarcts with reperfusion at the 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cold Temperature*
  • Coronary Vessels
  • Cryosurgery / instrumentation*
  • Disease Models, Animal*
  • Echocardiography
  • Hypertrophy, Right Ventricular / diagnostic imaging
  • Hypertrophy, Right Ventricular / pathology
  • Hypertrophy, Right Ventricular / physiopathology
  • Ligation
  • Mice
  • Mice, Inbred C57BL*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Pulmonary Edema / physiopathology
  • Survival Rate
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Pressure