Journal article
Calcium-dependent arrhythmias in transgenic mice with heart failure
American journal of physiology. Heart and circulatory physiology, Vol.284(2), pp.H431-H441
02/01/2003
DOI: 10.1152/ajpheart.00431.2002
PMID: 12388316
Abstract
Transgenic mice overexpressing the inflammatory cytokine tumor necrosis factor (TNF)-α (TNF-α mice) in the heart 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 with nontransgenic littermates. Programmed stimulation in vitro with single extra beats elicits reentrant ventricular arrhythmias in TNF-α ( n = 12 of 13 hearts) but not in control hearts. We performed optical mapping of voltage and Ca2+ in isolated perfused ventricles of TNF-α mice to study the mechanisms that lead to the initiation and maintenance of the arrhythmias. When compared with controls, hearts from TNF-α mice have prolonged of action potential durations (action potential duration at 90% repolarization: 23 ± 2 ms, n = 7, vs. 18 ± 1 ms, n = 5; P < 0.05), no increased dispersion of refractoriness between 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.
Details
- Title: Subtitle
- Calcium-dependent arrhythmias in transgenic mice with heart failure
- Creators
- Barry London - Cardiovascular Institute andLinda C Baker - Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh 15213; andJoon S Lee - Cardiovascular Institute andVladimir Shusterman - Cardiovascular Institute andBum-Rak Choi - Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh 15213; andToru Kubota - Cardiovascular Institute andCharles F McTiernan - Cardiovascular Institute andArthur M Feldman - Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Guy Salama - Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh 15213; and
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.284(2), pp.H431-H441
- DOI
- 10.1152/ajpheart.00431.2002
- PMID
- 12388316
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 02/01/2003
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025356302771
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