AJP - Heart AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (October 17, 2002). doi:10.1152/ajpheart.00431.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/2/H431    most recent
00431.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by London, B.
Right arrow Articles by Salama, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by London, B.
Right arrow Articles by Salama, G.

Articles in PresS, published online ahead of print October 17, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00431.2002
Submitted on May 21, 2002
Accepted on October 8, 2002

Calcium-Dependent Arrhythmias in Transgenic Mice with Heart Failure

Barry London1*, Linda C Baker2, Joon S Lee3, Vladimir Shusterman3, Bum-Rak Choi2, Toru Kubota3, Charles F McTiernan3, Arthur M Feldman4, and Guy Salama2

1 Department of Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA
2 Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA
3 Department of Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, USA
4 Department of Medicine, Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: londonb{at}msx.upmc.edu.

Transgenic mice overexpressing the inflammatory cytokine TNF-{alpha} in the heart (TNF-{alpha} mice) develop a progressive heart failure syndrome characterized by biventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias on ambulatory telemetry monitoring, and decreased survival compared to non-transgenic littermates. Programmed stimulation in-vitro with single extra beats elicits reentrant ventricular arrhythmias in TNF-{alpha} (n=12/13) but not control hearts. We performed optical mapping of voltage and Ca2+ in isolated perfused ventricles of TNF-{alpha} mice to study the mechanisms that lead to the initiation and maintenance of the arrhythmias. Compared to controls, hearts from TNF-{alpha}mice have prolonged of action potential durations (APD90 23±2 ms, n=7, vs 18±1 ms, n=5; p<0.05), no increased dispersion of refractoriness between the apex and base, elevated diastolic and depressed systolic Ca2+], and prolonged Ca2+ transients (72±6 ms, n=10, vs. 54±5 ms, n=8; p<0.01). Premature beats have diminished action potential amplitudes and conduct in a slow, heterogeneous manner. Lowering extracellular [Ca2+] normalizes conduction and prevents inducible arrhythmias. Thus, both action potential prolongation and abnormal Ca2+ handling may contribute to the initiation of reentrant arrhythmias in this heart failure model by mechanisms distinct from enhanced dispersion of refractoriness or triggered activity.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
G. S. Hoeker, R. P. Katra, L. D. Wilson, B. N. Plummer, and K. R. Laurita
Spontaneous calcium release in tissue from the failing canine heart
Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1235 - H1242.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
V. E. Bondarenko and R. L. Rasmusson
Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Fernandez-Velasco, G. Ruiz-Hurtado, O. Hurtado, M. A. Moro, and C. Delgado
TNF-{alpha} downregulates transient outward potassium current in rat ventricular myocytes through iNOS overexpression and oxidant species generation
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H238 - H245.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. E. Sawaya, Y. S. Rajawat, T. G. Rami, G. Szalai, R. L. Price, N. Sivasubramanian, D. L. Mann, and D. S. Khoury
Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor
Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1561 - H1567.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
G. Salama and B. London
Mouse models of long QT syndrome
J. Physiol., January 1, 2007; 578(1): 43 - 53.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
B. London, L. C. Baker, P. Petkova-Kirova, J. M. Nerbonne, B.-R. Choi, and G. Salama
Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT
J. Physiol., January 1, 2007; 578(1): 115 - 129.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
P. S. Petkova-Kirova, E. Gursoy, H. Mehdi, C. F. McTiernan, B. London, and G. Salama
Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-{alpha}
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H2098 - H2107.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Saba, A. M. Janczewski, L. C. Baker, V. Shusterman, E. C. Gursoy, A. M. Feldman, G. Salama, C. F. McTiernan, and B. London
Atrial contractile dysfunction, fibrosis, and arrhythmias in a mouse model of cardiomyopathy secondary to cardiac-specific overexpression of tumor necrosis factor-{alpha}
Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1456 - H1467.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
R. Balasubramaniam, S. Chawla, A. A. Grace, and C. L.-H. Huang
Caffeine-induced arrhythmias in murine hearts parallel changes in cellular Ca2+ homeostasis
Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1584 - H1593.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
I. R. Efimov, V. P. Nikolski, and G. Salama
Optical Imaging of the Heart
Circ. Res., July 9, 2004; 95(1): 21 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. M Janczewski, M. Zahid, B. H Lemster, C. S Frye, G. Gibson, Y. Higuchi, E. G Kranias, A. M Feldman, and C. F McTiernan
Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model
Cardiovasc Res, June 1, 2004; 62(3): 468 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
C. T. Maguire, H. Wakimoto, V. V. Patel, P. E. Hammer, K. Gauvreau, and C. I. Berul
Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies
Physiol Genomics, September 29, 2003; 15(1): 84 - 91.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. C. Knollmann, P. Kirchhof, S. G. Sirenko, H. Degen, A. E. Greene, T. Schober, J. C. Mackow, L. Fabritz, J. D. Potter, and M. Morad
Familial Hypertrophic Cardiomyopathy-Linked Mutant Troponin T Causes Stress-Induced Ventricular Tachycardia and Ca2+-Dependent Action Potential Remodeling
Circ. Res., March 7, 2003; 92(4): 428 - 436.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.