(Circulation. 1996;94:1109-1117.)
© 1996 American Heart Association, Inc.
Articles |
Transthoracic Echocardiography in Models of Cardiac Disease in the Mouse
the Division of Cardiology, Department of Medicine (N.T., N.D., L.M., H.A.R., K.L.P., K.R.G., J.J.H., K.R.C., J.R.), and the American Heart Association–Bugher Foundation Center for Molecular Biology (J.J.H., K.R.C., J.R.), University of California at San Diego.
Correspondence to John Ross, Jr, MD, Department of Medicine 0613B, University of California at San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0613. E-mail jross@ucsd.edu.
Background Transthoracic echocardiography (M-mode and Doppler) offers a noninvasive approach for in vivo evaluation of the mouse heart. The present study examines its usefulness for assessing the morphological/functional phenotype of the left ventricle (LV) in several transgenic and surgical murine models of cardiac disease.
Methods and Results Observations were made in 83 intact, anesthetized mice. In mice with a surgical arteriovenous fistula, volume overload and LV dilation were detected. In normal mice, echocardiographic indexes of increased contractility (dobutamine) were confirmed by LV dP/dtmax. In transgenic mice with overexpression of the ß2-adrenergic receptor, heart rate and mean velocity of circumferential fiber shortening were increased, indicating enhanced contractility. In colony screening of transgenic mice overexpressing the H-ras gene, 45% had increased LV wall thickness (>0.9 mm), and those showing a striking increase were selected for breeding. In mice with LV hypertrophy (aortic constriction) and normal mice, the actual LV mass determined by echocardiography correlated well (r=.93), and 95% confidence limits were determined. The maximum intraobserver and interobserver coefficients of variation for M-mode data were 0.03±0.29 mm (±2 SD), <10% for LV internal dimensions but 27% to 30% for wall thickness.
Conclusions These studies provide the first application of transthoracic echocardiography for morphological/functional characterization of the cardiac phenotype in transgenic and surgical murine models, including (1) high reliability for detecting LV chamber dilation and function; (2) reliability (and its limits) for determining abnormal LV wall thickness and LV mass; (3) identification of marked, sometimes asymmetrical, hypertrophy in a transgenic model of hypertrophic cardiomyopathy; and (4) usefulness for transgenic colony screening to identify markedly abnormal phenotypes.
Key Words: contractility • echocardiography • genes • hypertrophy • ventricles
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K. Suehiro, S. Takuma, C. Cardinale, T. Hozumi, J. Shimizu, H. Yano, M. R. Di Tullio, J. Wang, C. R. Smith, D. Burkhoff, et al. Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1729 - H1735. [Abstract] [Full Text] [PDF]
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F. Wiesmann, J. Ruff, S. Engelhardt, L. Hein, C. Dienesch, A. Leupold, R. Illinger, A. Frydrychowicz, K.-H. Hiller, E. Rommel, et al. Dobutamine-Stress Magnetic Resonance Microimaging in Mice : Acute Changes of Cardiac Geometry and Function in Normal and Failing Murine Hearts Circ. Res., March 30, 2001; 88(6): 563 - 569. [Abstract] [Full Text] [PDF]
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H.-S. Liao, P. M. Kang, H. Nagashima, N. Yamasaki, A. Usheva, B. Ding, B. H. Lorell, and S. Izumo Cardiac-Specific Overexpression of Cyclin-Dependent Kinase 2 Increases Smaller Mononuclear Cardiomyocytes Circ. Res., March 2, 2001; 88(4): 443 - 450. [Abstract] [Full Text] [PDF]
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X.-J. Du, X.-M. Gao, B. Wang, G. L Jennings, E. A Woodcock, and A. M Dart Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing {beta}2-adrenergic receptors in the heart Cardiovasc Res, December 1, 2000; 48(3): 448 - 454. [Abstract] [Full Text] [PDF]
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X.-J. Du, X.-M. Gao, G. L. Jennings, A. M. Dart, and E. A. Woodcock Preserved ventricular contractility in infarcted mouse heart overexpressing beta 2-adrenergic receptors Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2456 - H2463. [Abstract] [Full Text] [PDF]
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P.-H. Chu, W. M. Bardwell, Y. Gu, J. Ross Jr., and J. Chen FHL2 (SLIM3) Is Not Essential for Cardiac Development and Function Mol. Cell. Biol., October 15, 2000; 20(20): 7460 - 7462. [Abstract] [Full Text]
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S. M. Weis, J. L. Emery, K. D. Becker, D. J. McBride Jr, J. H. Omens, and A. D. McCulloch Myocardial Mechanics and Collagen Structure in the Osteogenesis Imperfecta Murine (oim) Circ. Res., October 13, 2000; 87(8): 663 - 669. [Abstract] [Full Text] [PDF]
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M. D. Feldman, J. M. Erikson, Y. Mao, C. E. Korcarz, R. M. Lang, and G. L. Freeman Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1698 - H1707. [Abstract] [Full Text] [PDF]
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 M. L. Marro, O. U. Scremin, M. C. Jordan, L. Huynh, F. Porro, K. P. Roos, S. Gajovic, F. E. Baralle, and A. F. Muro Hypertension in {beta}-Adducin-Deficient Mice Hypertension, September 1, 2000; 36(3): 449 - 453. [Abstract] [Full Text] [PDF]
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S. Rao and A. S. Verkman Analysis of organ physiology in transgenic mice Am J Physiol Cell Physiol, July 1, 2000; 279(1): C1 - C18. [Abstract] [Full Text] [PDF]
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 E. Bollano, E. Omerovic, M. Bohlooly-Y, V. Kujacic, B. Madhu, J. Tornell, O. Isaksson, B. Soussi, W. Schulze, M. L. X. Fu, et al. Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene Endocrinology, June 1, 2000; 141(6): 2229 - 2235. [Abstract] [Full Text] [PDF]
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L. Lipskaia, N. Defer, G. Esposito, I. Hajar, M.-C. Garel, H. A. Rockman, and J. Hanoune Enhanced Cardiac Function in Transgenic Mice Expressing a Ca2+-Stimulated Adenylyl Cyclase Circ. Res., April 14, 2000; 86(7): 795 - 801. [Abstract] [Full Text] [PDF]
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R. E. Henson, S. K. Song, J. S. Pastorek, J. J. H. Ackerman, and C. H. Lorenz Left ventricular torsion is equal in mice and humans Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1117 - H1123. [Abstract] [Full Text] [PDF]
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Y. Ikeda, M. Martone, Y. Gu, M. Hoshijima, A. Thor, S. S. Oh, K. L. Peterson, and J. Ross Jr. Altered membrane proteins and permeability correlate with cardiac dysfunction in cardiomyopathic hamsters Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1362 - H1370. [Abstract] [Full Text] [PDF]
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W. J. Karlon, A. D. McCulloch, J. W. Covell, J. J. Hunter, and J. H. Omens Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression of ras Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H898 - H906. [Abstract] [Full Text] [PDF]
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X.-M. Gao, A. M Dart, E. Dewar, G. Jennings, and X.-J. Du Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice Cardiovasc Res, January 14, 2000; 45(2): 330 - 338. [Abstract] [Full Text] [PDF]
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X.-P. Yang, Y.-H. Liu, N.-E. Rhaleb, N. Kurihara, H. E. Kim, and O. A. Carretero Echocardiographic assessment of cardiac function in conscious and anesthetized mice Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1967 - H1974. [Abstract] [Full Text] [PDF]
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T. Ryoke, Y. Gu, L. Mao, M. Hongo, R. G. Clark, K. L. Peterson, and J. Ross Jr Progressive Cardiac Dysfunction and Fibrosis in the Cardiomyopathic Hamster and Effects of Growth Hormone and Angiotensin-Converting Enzyme Inhibition Circulation, October 19, 1999; 100(16): 1734 - 1743. [Abstract] [Full Text] [PDF]
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M. Scherrer-Crosbie, W. Steudel, R. Ullrich, P. R. Hunziker, N. Liel-Cohen, J. Newell, J. Zaroff, W. M. Zapol, and M. H. Picard Echocardiographic determination of risk area size in a murine model of myocardial ischemia Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H986 - H992. [Abstract] [Full Text] [PDF]
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L. E. Rohde, A. Ducharme, L. H. Arroyo, M. Aikawa, G. H. Sukhova, A. Lopez-Anaya, K. F. McClure, P. G. Mitchell, P. Libby, and R. T. Lee Matrix Metalloproteinase Inhibition Attenuates Early Left Ventricular Enlargement After Experimental Myocardial Infarction in Mice Circulation, June 15, 1999; 99(23): 3063 - 3070. [Abstract] [Full Text] [PDF]
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S. Minamisawa, Y. Gu, J. Ross Jr., K. R. Chien, and J. Chen A Post-transcriptional Compensatory Pathway in Heterozygous Ventricular Myosin Light Chain 2-Deficient Mice Results in Lack of Gene Dosage Effect during Normal Cardiac Growth or Hypertrophy J. Biol. Chem., April 9, 1999; 274(15): 10066 - 10070. [Abstract] [Full Text] [PDF]
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K. H. Desai, E. Schauble, W. Luo, E. Kranias, and D. Bernstein Phospholamban deficiency does not compromise exercise capacity Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1172 - H1177. [Abstract] [Full Text] [PDF]
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M. H. Gao, N. C. Lai, D. M. Roth, J. Zhou, J. Zhu, T. Anzai, N. Dalton, and H. K. Hammond Adenylylcyclase Increases Responsiveness to Catecholamine Stimulation in Transgenic Mice Circulation, March 30, 1999; 99(12): 1618 - 1622. [Abstract] [Full Text] [PDF]
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M. Scherrer-Crosbie, W. Steudel, P. R. Hunziker, G. P. Foster, L. Garrido, N. Liel-Cohen, W. M. Zapol, and M. H. Picard Determination of Right Ventricular Structure and Function in Normoxic and Hypoxic Mice : A Transesophageal Echocardiographic Study Circulation, September 8, 1998; 98(10): 1015 - 1021. [Abstract] [Full Text] [PDF]
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N. Tanaka, T. Ryoke, M. Hongo, L. Mao, H. A. Rockman, R. G. Clark, and J. Ross Jr. Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H393 - H399. [Abstract] [Full Text] [PDF]
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P. A Doevendans, M. J. Daemen, E. D de Muinck, and J. F Smits Cardiovascular phenotyping in mice Cardiovasc Res, July 1, 1998; 39(1): 34 - 49. [Abstract] [Full Text] [PDF]
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P. D Verdouw, M. A van den Doel, S. de Zeeuw, and D. J Duncker Animal models in the study of myocardial ischaemia and ischaemic syndromes Cardiovasc Res, July 1, 1998; 39(1): 121 - 135. [Full Text] [PDF]
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H. A. Rockman, K. R. Chien, D.-J. Choi, G. Iaccarino, J. J. Hunter, J. Ross Jr., R. J. Lefkowitz, and W. J. Koch Expression of a beta -adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice PNAS, June 9, 1998; 95(12): 7000 - 7005. [Abstract] [Full Text] [PDF]
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R. D. Patten, M. J. Aronovitz, L. Deras-Mejia, N. G. Pandian, G. G. Hanak, J. J. Smith, M. E. Mendelsohn, and M. A. Konstam Ventricular remodeling in a mouse model of myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1812 - H1820. [Abstract] [Full Text] [PDF]
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R. V. Williams, J. N. Lorenz, S. A. Witt, D. T. Hellard, P. R. Khoury, and T. R. Kimball End-systolic stress-velocity and pressure-dimension relationships by transthoracic echocardiography in mice Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1828 - H1835. [Abstract] [Full Text] [PDF]
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J. F. James, T. E. Hewett, and J. Robbins Cardiac Physiology in Transgenic Mice Circ. Res., March 9, 1998; 82(4): 407 - 415. [Abstract] [Full Text] [PDF]
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F. Franco, S. K. Dubois, R. M. Peshock, and R. V. Shohet Magnetic resonance imaging accurately estimates LV mass in a transgenic mouse model of cardiac hypertrophy Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H679 - H683. [Abstract] [Full Text] [PDF]
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T. Kameyama, Z. Chen, S. P. Bell, J. Fabian, and M. M. Lewinter Mechanoenergetic studies in isolated mouse hearts Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H366 - H374. [Abstract] [Full Text] [PDF]
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P. M. Oliver, J. E. Fox, R. Kim, H. A. Rockman, H.-S. Kim, R. L. Reddick, K. N. Pandey, S. L. Milgram, O. Smithies, and N. Maeda Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A PNAS, December 23, 1997; 94(26): 14730 - 14735. [Abstract] [Full Text] [PDF]
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T. Kubota, C. F. McTiernan, C. S. Frye, S. E. Slawson, B. H. Lemster, A. P. Koretsky, A. J. Demetris, and A. M. Feldman Dilated Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Tumor Necrosis Factor-{alpha} Circ. Res., October 19, 1997; 81(4): 627 - 635. [Abstract] [Full Text]
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