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Articles |
In Vivo Echocardiographic Detection of Enhanced Left Ventricular Function in Gene-Targeted Mice With Phospholamban Deficiency
From the Division of Cardiology (B.D.H., S.F.K., N.B., R.A.W.) and the Department of Pharmacology and Cell Biophysics (E.G.K.), University of Cincinnati (Ohio).
Abstract We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) function reliably and repeatedly in mice and tested whether these techniques could detect physiological alterations in phospholamban (PLB)–deficient mice. Anesthetized wild-type mice (n=7) and mice deficient in PLB (n=8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in the baseline state and after intraperitoneal isoproterenol administration (2.0 µg/g IP). Interobserver and intraobserver variability and reproducibility were excellent. PLB-deficient mice were associated with significant (P<.05) increases in several physiological parameters (mean±SD) compared with wild-type control mice: normalized mean velocity of circumferential shortening (7.7±2.1 versus 5.5±1.0 circ/sec), peak aortic velocity (105±13 versus 75±9.2 cm/s), mean aortic acceleration (57±16 versus 31±4 m/s2), and peak early-diastolic transmitral velocity (80.0±7.2 versus 66.9±7.7 cm/s). LV dimensions, shortening fractions, heart rates, late diastolic transmitral (A) velocities, and early to late (E/A) diastolic velocity ratios were similar in both groups. Isoproterenol administration resulted in significant increases in Doppler indices of ventricular function in control but not PLB-deficient mice. These findings indicate that assessment of LV function can be performed noninvasively in mice under varying physiological conditions and that PLB regulates basal LV function in vivo.
Key Words: echocardiography • gene targeting • phospholamban • sarcoplasmic reticulum • left ventricular function
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J. N. Lorenz and E. G. Kranias Regulatory effects of phospholamban on cardiac function in intact mice Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2826 - H2831. [Abstract] [Full Text] [PDF]
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B. D. Hoit, N. Ball, and R. A. Walsh Invasive hemodynamics and force-frequency relationships in open- versus closed-chest mice Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2528 - H2533. [Abstract] [Full Text] [PDF]
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G. Chu, G. W. Dorn II, W. Luo, J. M. Harrer, V. J. Kadambi, R. A. Walsh, and E. G. Kranias Monomeric Phospholamban Overexpression in Transgenic Mouse Hearts Circ. Res., October 19, 1997; 81(4): 485 - 492. [Abstract] [Full Text]
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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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G. D. Pennock, D. D. Yun, P. G. Agarwal, P. H. Spooner, and S. Goldman Echocardiographic changes after myocardial infarction in a model of left ventricular diastolic dysfunction Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H2018 - H2029. [Abstract] [Full Text] [PDF]
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H. Wakasaki, D. Koya, F. J. Schoen, M. R. Jirousek, D. K. Ways, B. D. Hoit, R. A. Walsh, and G. L. King Targeted overexpression of protein kinase C beta 2 isoform in myocardium causes cardiomyopathy PNAS, August 19, 1997; 94(17): 9320 - 9325. [Abstract] [Full Text] [PDF]
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R. J. Hajjar, U. Schmidt, J. X. Kang, T. Matsui, and A. Rosenzweig Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes : Rescue Effects by Concomitant Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., August 19, 1997; 81(2): 145 - 153. [Abstract] [Full Text]
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D. D. D'Angelo, Y. Sakata, J. N. Lorenz, G. P. Boivin, R. A. Walsh, S. B. Liggett, and G. W. Dorn II Transgenic Galpha q overexpression induces cardiac contractile failure in mice PNAS, July 22, 1997; 94(15): 8121 - 8126. [Abstract] [Full Text] [PDF]
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K. R. Gottshall, J. J. Hunter, N. Tanaka, N. Dalton, K. D. Becker, J. Ross Jr., and K. R. Chien Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice PNAS, April 29, 1997; 94(9): 4710 - 4715. [Abstract] [Full Text] [PDF]
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K. L. Koss and E. G. Kranias Phospholamban: A Prominent Regulator of Myocardial Contractility Circ. Res., December 1, 1996; 79(6): 1059 - 1063. [Full Text]
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S. F. Khoury, B. D. Hoit, V. Dave, C. M. Pawloski-Dahm, Y. Shao, M. Gabel, M. Periasamy, and R. A. Walsh Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca2+-Cycling Proteins in the Baboon: Implications for the Force-Frequency and Relaxation-Frequency Relationships Circ. Res., October 1, 1996; 79(4): 727 - 735. [Abstract] [Full Text]
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N. Tanaka, N. Dalton, L. Mao, H. A. Rockman, K. L. Peterson, K. R. Gottshall, J. J. Hunter, K. R. Chien, and J. Ross Transthoracic Echocardiography in Models of Cardiac Disease in the Mouse Circulation, September 1, 1996; 94(5): 1109 - 1117. [Abstract] [Full Text]
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M. Iwase, S. P. Bishop, M. Uechi, D. E. Vatner, R. P. Shannon, R. K. Kudej, D. C. Wight, T. E. Wagner, Y. Ishikawa, C. J. Homcy, et al. Adverse Effects of Chronic Endogenous Sympathetic Drive Induced by Cardiac Gs{alpha} Overexpression Circ. Res., April 1, 1996; 78(4): 517 - 524. [Abstract] [Full Text]
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K. D. Becker, K. R. Gottshall, and K. R. Chien Strategies for Studying Cardiovascular Phenotypes in Genetically Manipulated Mice Hypertension, March 1, 1996; 27(3): 495 - 501. [Abstract] [Full Text]
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G. Chu, J. W. Lester, K. B. Young, W. Luo, J. Zhai, and E. G. Kranias A Single Site (Ser16) Phosphorylation in Phospholamban Is Sufficient in Mediating Its Maximal Cardiac Responses to beta -Agonists J. Biol. Chem., December 1, 2000; 275(49): 38938 - 38943. [Abstract] [Full Text] [PDF]
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B. C. Knollmann, S. A. Blatt, K. Horton, F. de Freitas, T. Miller, M. Bell, P. R. Housmans, N. J. Weissman, M. Morad, and J. D. Potter Inotropic Stimulation Induces Cardiac Dysfunction in Transgenic Mice Expressing a Troponin T (I79N) Mutation Linked to Familial Hypertrophic Cardiomyopathy J. Biol. Chem., March 23, 2001; 276(13): 10039 - 10048. [Abstract] [Full Text] [PDF]
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K. Haghighi, A. G. Schmidt, B. D. Hoit, A. G. Brittsan, A. Yatani, J. W. Lester, J. Zhai, Y. Kimura, G. W. Dorn II, D. H. MacLennan, et al. Superinhibition of Sarcoplasmic Reticulum Function by Phospholamban Induces Cardiac Contractile Failure J. Biol. Chem., June 22, 2001; 276(26): 24145 - 24152. [Abstract] [Full Text] [PDF]
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B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation Circ. Res., May 3, 2002; 90(8): 882 - 888. [Abstract] [Full Text] [PDF]
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