MR tagging early after myocardial infarction in mice demonstrates contractile dysfunction in adjacent and remote regions

Abstract

The purpose of this study was to use MR myocardial tagging to assess regional cardiac function after myocardial infarction (MI) in mice. Eight mice were imaged before and 1 day after MI. MRI included cine imaging, myocardial tagging, and contrast-enhanced imaging. Regional percent circumferential shortening (%CS) was measured from the tagged images, and the region of hyperenhancement on the contrast-enhanced images was used to determine the infarcted, adjacent, and remote zones. Ejection fraction (EF) fell from 59% ؎ 6% at baseline to 32% ؎ 6% after MI (P < 0.01). At baseline, %CS was 14.5% ؎ 3.4%. After MI, %CS was 0.7% ؎ 4.4% in the infarcted zone, 7.4% ؎ 4.4% in the adjacent zone, and 11.8% ؎ 4.2% in the remote zone. %CS was statistically different for all comparisons between the infarcted, adjacent, remote, and baseline groups (P < 0.01 Transgenic and knockout mice can be used to study the genes and basic mechanisms involved in cardiovascular disease, and have therefore assumed a central role in modern cardiovascular research. Over the past 3 years, MRI has emerged as an accurate, noninvasive imaging modality for measuring murine cardiac structure and function in vivo (1-3). Examples demonstrating cardiac MRI in transgenic mouse research include studies of myocardial infarction (MI) (4) and left ventricular (LV) remodeling (5). To date, such studies have used MRI to measure myocardial mass, end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). While such measures of global cardiac function are very useful, in the setting of coronary heart disease (where contractile dysfunction is generally localized to specific coronary territories) it is critically important to evaluate myocardial function on a regional basis. In the current study, we sought to demonstrate that myocardial tagging (6,7) could be used to measure regional contractile function in a mouse model of reperfused MI. METHODS Animal PreparationNine C57BL/6 mice were used in this study, which was approved by the University of Virginia Animal Care and Use Committee. MI was surgically induced as described previously (8). Briefly, mice were anesthetized, the upper portion of the trachea was exposed, and an endotracheal tube was inserted orally. Artificial respiration was maintained with an SAR-830/P ventilator (FiO2 of 0.80, rate of 100 strokes/min, stroke volume 2.0 -2.5 ml). After intubation, an incision was made to open the left pleural cavity. A piece of 7-0 silk suture was passed underneath the left anterior descending coronary artery (LAD) at the level of the lower left atrium and myocardial ischemia was induced by tying down the suture over PE-10 tubing. After 60 min of LAD occlusion, reperfusion was achieved by loosening the suture. Significant ECG changes (widening of the QRS wave and ST segment elevation as monitored with a PowerLab data recorder) and blanching within the region at risk were used to confirm coronary occlusion. A volume of 1-1.5 ml 5% dextrose was given intraperitoneally (i.p.) to replace fluids. Body...

Magnetic resonance imaging of regional cardiac function in the mouse

“…From this we conclude that the area is still active and not infarcted but has an atypical contraction pattern. The circumferential strain outside the infarcted region is within the range of previously reported values [12,34].…”

“…3 and 4 show that there was no uniform distribution of strain values over the left ventricular wall of the infarcted mouse heart. The measured mean circumferential strain of the healthy mouse heart is lower than reported in the literature [12,34], which might be explained by differences in mouse strain. Although a detailed analysis of the regional strains in relation to the induced infarction is beyond the scope of this paper, it is noteworthy that the circumferential strain in the slice above the infarction (Fig.…”

“…Their study, however, differs from our study by a difference in the adaptation time following infarction, 4 days versus 1 day, and a difference in the mouse model, reperfusion versus permanent occlusion. The mean circumferential strains in the infarcted region were lower than found in other studies [12,34]. These differences might be caused by differences in the measuring position and differences in the extent of the induced infarction.…”

“…This might be explained by the fact that different regions of the mouse heart are going through a process of differential remodeling and adaptation such as also observed in humans [51,52] and canines [53]. In contrast, Epstein et al [12] have found impairment of the remote myocardium in mice. Their study, however, differs from our study by a difference in the adaptation time following infarction, 4 days versus 1 day, and a difference in the mouse model, reperfusion versus permanent occlusion.…”

“…Regional tissue viability can be assessed with perfusion MR, e.g., using arterial spin labeling techniques [8], or from the delayed enhancement effect following gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) injection [9]. Phase velocity [10] and tagging techniques [11][12][13][14] are able to measure local wall motion and muscle fiber shortening, which provide important insights into local tissue function. The metabolic state of the heart tissue can be determined using 31 P-, 13 C-, or 23 Na magnetic resonance spectroscopy (MRS) [15][16][17], or by MRI measurements of the local influx of Mn 2+ , which acts as an MRI contrast agent and can be considered a calcium analogue [18].…”