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

Fatima Franco, Gail D. Thomas, Brett Giroir, Debora Bryant, M. Craig Bullock, Michael P Chwialkowski, Ronald G. Victor, Ronald M Peshock

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Background - Transgenic mice expressing tumor necrosis factor-α (TNF- α) 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-α? Methods and Results - Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-α 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, 195X 195 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; SVTD(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 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-α mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF-α overexpression.

Original languageEnglish (US)
Pages (from-to)448-454
Number of pages7
JournalCirculation
Volume99
Issue number3
StatePublished - Jan 26 1999

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Transgenic Mice
Heart Failure
Tumor Necrosis Factor-alpha
Magnetic Resonance Imaging
Thermodilution
Cardiac Output
Cine Magnetic Resonance Imaging
Cardiac Volume
Ventricular Remodeling
Dilated Cardiomyopathy
Left Ventricular Dysfunction
Cardiac Myocytes
Stroke Volume

Keywords

  • Cardiac output
  • Heart failure
  • Magnetic resonance imaging
  • Systole

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Magnetic resonance imaging and invasive evaluation of development of heart failure in transgenic mice with myocardial expression of tumor necrosis factor-α. / Franco, Fatima; Thomas, Gail D.; Giroir, Brett; Bryant, Debora; Bullock, M. Craig; Chwialkowski, Michael P; Victor, Ronald G.; Peshock, Ronald M.

In: Circulation, Vol. 99, No. 3, 26.01.1999, p. 448-454.

Research output: Contribution to journalArticle

Franco, Fatima ; Thomas, Gail D. ; Giroir, Brett ; Bryant, Debora ; Bullock, M. Craig ; Chwialkowski, Michael P ; Victor, Ronald G. ; Peshock, Ronald M. / Magnetic resonance imaging and invasive evaluation of development of heart failure in transgenic mice with myocardial expression of tumor necrosis factor-α. In: Circulation. 1999 ; Vol. 99, No. 3. pp. 448-454.
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AU - Franco, Fatima

AU - Thomas, Gail D.

AU - Giroir, Brett

AU - Bryant, Debora

AU - Bullock, M. Craig

AU - Chwialkowski, Michael P

AU - Victor, Ronald G.

AU - Peshock, Ronald M

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N2 - Background - Transgenic mice expressing tumor necrosis factor-α (TNF- α) 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-α? Methods and Results - Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-α 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, 195X 195 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; SVTD(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 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-α mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF-α overexpression.

AB - Background - Transgenic mice expressing tumor necrosis factor-α (TNF- α) 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-α? Methods and Results - Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-α 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, 195X 195 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; SVTD(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 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-α mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF-α overexpression.

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