New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction

PLoS One. 2012;7(7):e41691. doi: 10.1371/journal.pone.0041691. Epub 2012 Jul 27.

Abstract

Background: The aim of this article is to present an optimized acquisition and analysis protocol for the echocardiographic evaluation of left ventricle (LV) remodeling in a mouse model of myocardial infarction (MI).

Methodology: 13 female DBA/2J mice underwent permanent occlusion of the left anterior descending (LAD) coronary artery leading to MI. Mice echocardiography was performed using a Vevo 770 (Visualsonics, Canada) before infarction, and 7, 14, 30, 60, 90 and 120 days after LAD ligation. LV systolic function was evaluated using different parameters, including the fractional area change (FAC%) computed in four high-temporal resolution B-mode short axis images taken at different ventricular levels, and in one parasternal long axis. Pulsed wave and tissue Doppler modes were used to evaluate the diastolic function and Tei Index for global cardiac function. The echocardiographic measurements of infarct size were validated histologically using collagen deposition labeled by Sirius red staining. All data was analyzed using Shapiro-Wilk and Student's t-tests.

Principal findings: Our results reveal LV dilation resulting in marked remodeling an severe systolic dysfunction, starting seven days after MI (LV internal apical diameter, basal = 2.82±0.24, 7d = 3.49±0.42; p<0.001. End-diastolic area, basal = 18.98±1.81, 7d = 22.04±2.11; p<0.001). A strong statistically significant negative correlation exists between the infarct size and long-axis FAC% (r = -0.946; R(2) = 0.90; p<0.05). Moreover, the measured Tei Index values confirmed significant post-infarction impairment of the global cardiac function (basal = 0.46±0.07, 7d = 0.55±0.08, 14 d = 0.57±0.06, 30 d = 0.54±0.06, 60 d = 0.54±0.07, 90 d = 0.57±0.08; p<0.01).

Conclusions/significance: In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Echocardiography / methods*
  • Female
  • Image Processing, Computer-Assisted
  • Mice
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Time Factors
  • Ventricular Function, Left / physiology*
  • Ventricular Remodeling

Grants and funding

This project was partially funded by the UTE Project CIMA, the subprogram for unique strategic projects of the Spanish Science and Innovation Ministry (MICINN PSS-010000-2008-2) and the Instituto de Salud Carlos III (ISCIII PI050168, PI10/01621, CP09/00333 and ISCIII-RETIC RD06/0014), Ministerio de Ciencia e Innovación (PLE2009-0116 and PSE SINBAD, PSS 0100000-2008-1). Carolina Benavides-Vallve is partially funded by the MICINN's program of Promotion of Technical Personal Support (PTA2008-1228-I). Arrate Muñoz -Barrutia holds a Ramón y Cajal Fellowship of the MICINN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.