Dobutamine stress cine-MRI of cardiac function in the hearts of adult cardiomyocyte-specific VEGF knockout mice.
A mouse model of non-necrotic vascular deficiency in the adult heart was studied using cine-magnetic resonance imaging (MRI) and other techniques. The mice lacked cardiomyocyte-derived vascular endothelial growth factor (VEGF) following a targeted knockout in the ventricular cardiomyocytes. Quantitative endothelial labeling showed that the capillary density was significantly reduced in the hearts of knockout mice. Gene expression patterns suggested that they were hypoxic. Semiautomated MR image analysis was employed to obtain both global and regional measurements of left ventricular function at 10 or more time points through the cardiac cycle. MRI measurements showed a marked reduction in ejection fraction both at rest and under low- and high-dose dobutamine stress. Regional wall thickness, thickening, and displacement were all attenuated in the knockout mice. A prolonged high-dose dobutamine challenge was monitored by MRI. A maximal response was sustained for 90 minutes, suggesting that it did not depend on endogenous glycogen stores.
Williams
S P
SP
Genentech, Inc., 1 DNA Way #72A, South San Francisco, CA 94080, USA. williams.simon@gene.com
Gerber
H P
HP
Giordano
F J
FJ
Peale
F V
FV
Bernstein
L J
LJ
Bunting
S
S
Chien
K R
KR
Ferrara
N
N
van Bruggen
N
N
D000818:Animals; D001835:Body Weight; D002196:Capillaries / Q000033:anatomy & histology; D004280:Dobutamine; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008962:Models, Theoretical; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004280:Dobutamine