(Circulation. 1996;94:2641-2648.)
© 1996 American Heart Association, Inc.
Articles |
In Vivo Cardiac Electrophysiology Studies in the Mouse
the Divisions of Pediatric Cardiology (C.I.B.) and Cardiology (M.J.A., P.J.W., M.E.M.) and the Molecular Cardiology Research Center (C.I.B., M.E.M.), New England Medical Center and Tufts University School of Medicine, Boston, Mass.
Correspondence to Charles I. Berul, MD, or Michael E. Mendelsohn, MD, Molecular Cardiology Research Center, Tufts–New England Medical Center, Box 80, 750 Washington St, Boston, MA 02111.
Background This report describes a novel in vivo mouse epicardial cardiac electrophysiology study based on clinical protocols used to evaluate cardiac conduction in human patients. The technique allows extensive electrophysiological evaluation, including the response to pacing, programmed stimulation, and pharmacological agents.
Methods and Results Surface six-lead ECG data from 18 C57BL/6J mice are presented. Normal cardiac conduction properties for 14 of 18 mice that underwent the procedure are summarized, including determination of sinus node recovery times, AV conduction properties, and atrial, AV, and ventricular effective refractory periods. A subset of six mice was studied after the administration of either procainamide (n=3) or quinidine (n=3). All animals in the procainamide group developed either second-degree or complete AV block spontaneously. The sinus cycle length and refractory periods prolonged on procainamide or quinidine, but no tachyarrhythmias could be induced with atrial or ventricular programmed stimulation.
Conclusions This mouse electrophysiology method allows rapid assessment of the conduction properties of the murine heart. The ability to analyze cardiac conduction in normal and transgenic mice provides a powerful tool for examining molecular electrophysiological mechanisms in normal physiology and disease states.
Key Words: electrophysiology • mice • genes • arrhythmia
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|
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|
|
|
|
|
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|
|
|
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|
|
|
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|
|
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|
|
|
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|
|
|
|
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|
|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
H. Wakimoto, C. T Maguire, P. Kovoor, P. E Hammer, J. Gehrmann, J. K Triedman, and C. I Berul Induction of atrial tachycardia and fibrillation in the mouse heart Cardiovasc Res, June 1, 2001; 50(3): 463 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
J. Gehrmann, P. E. Hammer, C. T. Maguire, H. Wakimoto, J. K. Triedman, and C. I. Berul Phenotypic screening for heart rate variability in the mouse Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H733 - H740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
A. Jeron, G. F. Mitchell, J. Zhou, M. Murata, B. London, P. Buckett, S. D. Wiviott, and G. Koren Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1891 - H1898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Baker, B. London, B.-R. Choi, G. Koren, and G. Salama Enhanced Dispersion of Repolarization and Refractoriness in Transgenic Mouse Hearts Promotes Reentrant Ventricular Tachycardia Circ. Res., March 3, 2000; 86(4): 396 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, S. Swirp, and H. Duff Age-dependent response of the electrocardiogram to K+ channel blockers in mice Am J Physiol Cell Physiol, January 1, 2000; 278(1): C73 - C80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H.T. Wehrens, S. Kirchhoff, and P. A. Doevendans Mouse electrocardiography: An interval of thirty years Cardiovasc Res, January 1, 2000; 45(1): 231 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Brown, D. M. Walters, R. S. Greenberg, and W. Mitzner A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice J Appl Physiol, December 1, 1999; 87(6): 2362 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vaidya, G. E. Morley, F. H. Samie, and J. Jalife Reentry and Fibrillation in the Mouse Heart : A Challenge to the Critical Mass Hypothesis Circ. Res., July 23, 1999; 85(2): 174 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hagendorff, B. Schumacher, S. Kirchhoff, B. Luderitz, and K. Willecke Conduction Disturbances and Increased Atrial Vulnerability in Connexin40-Deficient Mice Analyzed by Transesophageal Stimulation Circulation, March 23, 1999; 99(11): 1508 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kupershmidt, T. Yang, M. E. Anderson, A. Wessels, K. D. Niswender, M. A. Magnuson, and D. M. Roden Replacement by Homologous Recombination of the minK Gene With lacZ Reveals Restriction of minK Expression to the Mouse Cardiac Conduction System Circ. Res., February 5, 1999; 84(2): 146 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Babij, G. R. Askew, B. Nieuwenhuijsen, C.-M. Su, T. R. Bridal, B. Jow, T. M. Argentieri, J. Kulik, L. J. DeGennaro, W. Spinelli, et al. Inhibition of Cardiac Delayed Rectifier K+ Current by Overexpression of the Long-QT Syndrome HERG G628S Mutation in Transgenic Mice Circ. Res., September 21, 1998; 83(6): 668 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lee, G. Morley, Q. Huang, A. Fischer, S. Seiler, J. W. Horner, S. Factor, D. Vaidya, J. Jalife, and G. I. Fishman Conditional lineage ablation to model human diseases PNAS, September 15, 1998; 95(19): 11371 - 11376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Johansson, B. Vennstrom, and P. Thoren Evidence that decreased heart rate in thyroid hormone receptor-alpha 1-deficient mice is an intrinsic defect Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R640 - R646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S Mitcheson, J. C Hancox, and A. J Levi Cultured adult cardiac myocytes: Future applications, culture methods, morphological and electrophysiological properties Cardiovasc Res, August 1, 1998; 39(2): 280 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. L. Hill, J.-a. K. Evangelista, A. M. Pizzi, M. Mobassaleh, D. R. Fulton, and C. I. Berul Proarrhythmia Associated With Cisapride in Children Pediatrics, June 1, 1998; 101(6): 1053 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Fishman Timing Is Everything in Life : Conditional Transgene Expression in the Cardiovascular System Circ. Res., May 4, 1998; 82(8): 837 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. F. Mitchell, A. Jeron, and G. Koren Measurement of heart rate and Q-T interval in the conscious mouse Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H747 - H751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Thomas, R. B. Schuessler, C. I. Berul, M. A. Beardslee, E. C. Beyer, M. E. Mendelsohn, and J. E. Saffitz Disparate Effects of Deficient Expression of Connexin43 on Atrial and Ventricular Conduction : Evidence for Chamber-Specific Molecular Determinants of Conduction Circulation, February 24, 1998; 97(7): 686 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Chuck, D. M. Freeman, M. Watanabe, and D. S. Rosenbaum Changing Activation Sequence in the Embryonic Chick Heart : Implications for the Development of the His-Purkinje System Circ. Res., October 19, 1997; 81(4): 470 - 476. [Abstract] [Full Text]
|
|