MRI-based prediction of adverse cardiac remodeling after murine myocardial infarction

Abstract

Protti A, Dong X, Sirker A, Botnar R, Shah AM. MRI-based prediction of adverse cardiac remodeling after murine myocardial infarction. Am J Physiol Heart Circ Physiol 303: H309 -H314, 2012. First published May 25, 2012; doi:10.1152/ajpheart.00208.2012 results in adverse cardiac remodeling leading to heart failure and increased mortality. Experimental mouse models of MI are extensively used to identify mechanisms underlying adverse remodeling, but the extent of remodeling that occurs may be highly variable and can limit the utility to discover new disease pathways. The ability to predict the development of significant late post-MI remodeling would be invaluable in conducting such studies by increasing throughput and efficiency. This study aimed to identify potential thresholds of cardiac magnetic resonance imaging (MRI) parameters measured early after murine MI that would predict the development of significant adverse remodeling at 4 wk. MI was achieved by permanent coronary ligation and animals (n ϭ 84) were followed up for 4 wk subsequently. MRI was used to assess left ventricular (LV) volumes, mass and ejection fraction, as well as infarct size (IS). Late gadolinium enhancement cine-MRI was performed at 2 days with standard cine-MRI at 30 days post-MI. Utilizing multiple logistic regression, we found that IS Ͼ36%, at 2 days post-MI, was the overall best single predictor of adverse remodeling at 30 days (sensitivity 80.7%, specificity 88.9%; C-statistic of 0.939 from receiver-operating curve analysis). LV end-systolic volume (LVESV) Ͼ32 l was also an excellent predictor comparable to IS. The combination of IS Ͼ36% and/or LVESV Ͼ32 l provided the highest predictive values for late adverse remodeling among multiple predictors. This study demonstrates that MRIbased estimation of IS and ESV during the acute phase of murine MI are good predictors of subsequent adverse remodeling that may aid experimental design. remodeling prediction; magnetic resonance imaging; infarct size; ejection fraction MYOCARDIAL INFARCTION (MI) is commonly followed by adverse left ventricular (LV) remodeling involving significant changes in LV geometry and function (4). Such adverse remodeling contributes to impaired cardiac function and is a major cause of heart failure and increased mortality (25). Experimental models of MI, for example, as induced by permanent coronary ligation in gene-modified mice, are extensively utilized to elucidate pathophysiological and molecular mechanisms underlying cardiac remodeling that could be therapeutically targeted (5,17,18,22,23,27). The extent of adverse remodeling that occurs after experimental MI in murine models, as manifest by an increase in LV end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively) and a reduction in ejection fraction (EF), can be highly variable and can limit their utility to discover new disease pathways (23,29). This is most likely related to variations in the severity and extent of myocardial injury that is induced by coronary ligation in mouse models (15,23,28,2...

Using MRI to predict future adverse cardiac remodelling in a male mouse model of myocardial infarction

“…The extent of adverse remodelling as judged by EDV wk4 was directly proportional to LV-ESV wk1 with small infarcts increasing by the same proportion as larger infarcts . This finding is in contrast to a previous study using female mice which observed a biphasic response, with smaller infarcts showing no progression [9]. This difference could be due to gender differences in the mice used for the studies.…”

“…In contrast, cardiac MRI provides a powerful technique to measure heart function under transient anaesthesia and is considered the “gold standard” permitting longitudinal studies to track cardiac function in individual animals [8]. Using this technique Protti and colleagues recently investigated adverse cardiac remodelling following surgical ligation of the LAD in wild-type (C57BL/6) mice [9]. They observed that left ventricular end diastolic volume (LV-EDV) at an early stage (2 days) following MI was predictive of the adverse cardiac remodelling outcome at 30 days and that infarcted mice fell into two groups (i) progression and (ii) non-progression, with non-progression associated with small infarct size.…”

High-frequency speckle tracking echocardiography in the assessment of left ventricular function and remodeling after murine myocardial infarction

“…Therefore, MRI remains the gold standard for absolute quantification of LV volumes but STE-derived measures may have significant utility in serial assessment and for comparison among groups. Another clear advantage of MRI remains the direct determination of infarct size, which is often critical in experimental models in ensuring equal stimuli to postinfarct LV remodeling across different study groups (21,22). On the other hand, echocardiography has a number of other potential benefits over MRI, namely 1) greater availability to researchers in many institutions; 2) greater tolerability- some groups even use echo in conscious mice that have undergone training in order to allow this (32).…”

“…For the subgroup of mice in which infarct size was estimated, this was done from the 11 consecutive short-axis views from base to apex. The infarct size was calculated as the percentage midline length of thinned myocardium against the total LV midline length (21,22). Thinned myocardium was defined as a reduction in thickness by Ͼ60% compared with healthy myocardium, and the motionless properties of the tissue in MRI images during the cardiac cycle.…”

Update on innovative initiatives for the American Journal of Physiology-Heart and Circulatory Physiology

“…Among the eight articles in our review article collection on "Assessing Cardiovascular Function in Mice: New Developments and Methods" (18, 21, 37, 75), we covered advances in molecular imaging of atherosclerosis (73) and MRI and spectroscopy (1), as well as the continuing evolution of the Langendorff and ejecting murine heart (52) and innovative developments in small animal echocardiography (109). In our collection on "Cardiovascular Regulation in Pregnancy," we discussed the vascular effects of maternal alcohol consumption (76), the reduced uterine perfusion pressure model of preeclampsia in a rats (51), and an analysis of the adaptive changes of mesenteric arteries in pregnancy (95).…”