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(Circulation. 1999;99:448-454.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Magnetic Resonance Imaging and Invasive Evaluation of Development of Heart Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-

Fatima Franco, MD; Gail D. Thomas, PhD; Brett Giroir, MD; Debora Bryant, BS; M. Craig Bullock, BSEE; Michael C. Chwialkowski, PhD; Ronald G. Victor, MD; Ronald M. Peshock, MD

From the Departments of Radiology (F.F., R.M.P.), Internal Medicine (G.D.T., R.G.V., R.M.P.), and Pediatrics (B.G., D.B., R.M.P.) at the University of Texas Southwestern Medical Center at Dallas and the Department of Electrical Engineering (M.C.B., M.C.C.), University of Texas at Arlington.

Correspondence to Ronald M. Peshock, MD, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, University of Texas, Southwestern Medical Center, 5801 Forest Park, Dallas, TX 75235-9085. E-mail rpesho{at}mednet.swmed.edu

Background—Transgenic mice expressing tumor necrosis factor- (TNF-) 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-?

Methods and Results—Transgenic mice from 2 different lineages with differing amounts of myocardial TNF- 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 µm in-plane resolution). MRI CO and SV correlated well with TD [CO_TD (mL/min)=0.94*CO_MRI+0.72, r=0.84; SV_TD(µL)=1.01*SV_MRI-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- mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF- overexpression.

Key Words: heart failure • systole • magnetic resonance imaging • cardiac output

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