Abstract 130: The Diversity of Coronary Artery and Myocardial Infarction in Mice

Abstract

Low reliability and reproducibility in heart failure research has been a major concern. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. Methods: MI was induced by left coronary artery (LCA) ligation. Echocardiography was used to measure cardiac function after MI. The coronary artery was casted with resin and visualized with fluorescent imaging in ex vivo. LCA characteristics and MI size were analyzed individually in each animal. MI size was correlated with LV function by echocardiography. Results: Coronary anatomy varies widely amongst animals, posing challenges for surgical ligation and resulting in inconsistent MI size data post-ligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches were unique in every animal. When the main LCA trunk was ligated, this resulted in a large MI, but when a single branch was ligated, MI size varied significantly due to differing levels of LCA ligation and differing amounts of territory supplied by the branches. During the ligation procedure, nearly 40% of LCAs were not grossly visible to the surgeon. In these situations, the surgeon commonly blindly sutures a wider and deeper area of tissue in an attempt to ensure that the LCA is caught and ligated. Paradoxically, these situations have greater odds of resulting in smaller MIs. Conclusion: The current study offers evidence of anatomical LCA diversity and the problems this poses for creating a consistent heart failure model by LCA ligation in mice. Carefully recognizing the inevitable individual variation of coronary anatomy in mice is essential to restoring reliability of the LCA ligation model of heart failure.