MRI assessment of cardiac function in mice correlated well with invasive thermodilution (r=0.84 for cardiac output), demonstrating progressive LV dysfunction dependent on TNF-alpha overexpression.
MRI provides a reliable, non-invasive method to longitudinally assess cardiac function and progressive LV remodeling in a mouse model of TNF-alpha-induced heart failure.
Effect estimate: r=0.84 for cardiac output; r=0.94 for stroke volume
BACKGROUND: Transgenic mice expressing tumor necrosis factor-alpha (TNF-alpha) in cardiac myocytes develop dilated cardiomyopathy, but the temporal progression to cardiac dysfunction is not well characterized. We asked (1) Does magnetic resonance imaging (MRI) provide a reproducible assessment of cardiac output in mice that correlates with invasive measurements obtained with thermodilution? (2) What is the time course of left ventricular (LV) remodeling in transgenic mice with myocardial expression of TNF-alpha? METHODS AND RESULTS: Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-alpha expression lineage 1 (L1) and lineage 2 (L2) and littermate controls (LC) were studied. In protocol 1, cardiac output (CO) and stroke volume (SV) were measured by MRI and thermodilution (TD) in 15 mice (3 L1, 4 L2, 8 LC). In protocol 2, 23 mice (7 L1, 8 L2, 8 LC) were scanned at 1 month of life and every 4 weeks thereafter. In both protocols, cine-MRI was performed with the use of a 1.5-T clinical system (1.5-mm slices, 195x195 microm in-plane resolution). MRI CO and SV correlated well with TD COTD (mL/min)=0.94*COMRI+0.72, r=0.84; SVTD( microL)=1. 01*SVMRI-1.07, r=0.94. Serial MRI studies showed significant increase in LV mass and volumes over time and a significant decrease in ejection fraction in transgenic mice when compared with littermate controls. Compared with lineage 2, lineage 1 showed significantly larger LV mass and volumes and significantly lower ejection fraction. CONCLUSIONS: MRI assessment of cardiac function in mice correlates well with invasive measurements. Serial MRI studies in the TNF-alpha mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF-alpha overexpression.
Franco et al. (Tue,) conducted a other in Dilated cardiomyopathy (n=38). Myocardial expression of TNF-alpha vs. Littermate controls was evaluated on Correlation of cardiac output and stroke volume measured by MRI and thermodilution (r=0.84 for cardiac output; r=0.94 for stroke volume). MRI assessment of cardiac function in mice correlated well with invasive thermodilution (r=0.84 for cardiac output), demonstrating progressive LV dysfunction dependent on TNF-alpha overexpression.