Variability in coronary artery anatomy affects consistency of cardiac damage after myocardial infarction in mice

Abstract

Low reliability and reproducibility in heart failure models are well established. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. MI was induced by left coronary artery (LCA) ligation. The coronary artery was casted with resin and visualized with fluorescent imaging ex vivo. LCA characteristics and MI size were analyzed individually in each animal, and MI size was correlated with left ventricular (LV) function by echocardiography. Coronary anatomy varies widely in mice, posing challenges for surgical ligation and resulting in inconsistent MI size postligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches are unique in each animal. When the main LCA trunk is ligated, this results in a large MI, but when a single branch is ligated, MI size is variable due to differing levels of LCA ligation and area supplied by the branches. During the ligation procedure, nearly 40% of LCAs are not grossly visible to the surgeon. In these situations, the surgeon blindly sutures a wider and deeper area of tissue in an attempt to catch the LCA. Paradoxically, these situations have greater odds of resulting in smaller MIs. In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart failure research.

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“…Although left coronary artery (LCA) ligation is most commonly used to induce myocardial ischemia in mice, this surgical procedure has disadvantages of a high mortality rate and a large variation in infarct size 39. In contrast, ISO-induced myocardial ischemia is a simple, easy-to-operate modeling method that can reduce inconsistency in infarct size due to anatomic diversity of the LCA in mice 40. Recently, it has been reported that ISO has deleterious cardiac effects in rat, including apoptosis, mitochondrial alterations, fibrosis, oxidative damage, inflammatory cell infiltration, and morphological changes of cardiomyocytes, which is similar to that in the infarcted human heart 41,42.…”

Guidelines for measuring cardiac physiology in mice

“…To evaluate the current reporting of echocardiographic results, we accessed PubMed on July 21, 2017, and searched for “mouse and American Journal of Physiology and (echocardiography or echocardiographic or ultrasound).” This search resulted in 437 articles, of which 52 articles were published between January 1, 2016, and present as well as 14 articles that were excluded as false positives (two kidney, one liver, one lung, one bone, one RV, two rat not mouse, one fetal not adult, and five with no cardiac echocardiography results). The remaining 38 articles were analyzed both for completeness of information provided and for quality assessment of the echocardiography values reported ( 11 , 13 , 22 , 27 , 30 , 36 , 38 , 39 , 42 , 45 , 52 , 54 , 57 , 59 , 65 , 70 , 75 , 76 , 78 , 85 , 102 , 114 , 117 – 119 , 132 , 147 , 148 , 158 , 160 , 165 , 170 , 172 , 182 , 187 , 193 , 201 , 206 ).…”

Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response

“…After 45 min of ischemia, reperfusion was allowed for indicated time points. As previously described, different infarct sizes may be created by this method due to differences in mouse physiology 43,44 . Mice were treated with 0.1 mg/kg buprenorphine (Temgesic, CatNo.…”