Magnetic resonance imaging and invasive evaluation of development of heart failure in transgenic mice with myocardial expression of tumor necrosis factor-α

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 con-elates 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 1, weeks thereafter. In both protocols, cine-MRI was performed with the use of a 1.5-T clinical system (1.5-mm slices, 195x195 mu m in-plane resolution). MRI CO and SV correlated well with TD [COTD (mL/min)=0.94*COMRI+ 0.72, r=0.84; SVTD(mu L)=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. Conclusion-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.