Aging-related mitochondrial dysfunction facilitates the occurrence of serious arrhythmia after myocardial infarction

During aging a mosaic of normal cells and cells with mitochondrial deficiency develops in various tissues including the heart. Whether this contributes to higher susceptibility for arrhythmia following myocardial infarction (MI) is unknown. Myocardial cryoinfarction was performed in 12-month-old tra...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2017-11, Vol.493 (1), p.604-610
Main Authors: Stöckigt, Florian, Beiert, Thomas, Knappe, Vincent, Baris, Olivier R., Wiesner, Rudolf J., Clemen, Christoph S., Nickenig, Georg, Andrié, René P., Schrickel, Jan W.
Format: Article
Language:English
Subjects:
Aging
Animals
Arrhythmia
Arrhythmias, Cardiac - etiology
Arrhythmias, Cardiac - physiopathology
Female
Heart Conduction System - physiopathology
Infarction
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria
Mitochondria, Heart
Mitochondrial Diseases - complications
Mitochondrial Diseases - physiopathology
Myocardial Infarction - complications
Myocardial Infarction - physiopathology
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Summary:During aging a mosaic of normal cells and cells with mitochondrial deficiency develops in various tissues including the heart. Whether this contributes to higher susceptibility for arrhythmia following myocardial infarction (MI) is unknown. Myocardial cryoinfarction was performed in 12-month-old transgenic mice with accelerated accumulation of deletions in mitochondrial DNA. Occurrence and pathogenesis of arrhythmia was investigated after two weeks. Holter-ECG recordings revealed higher rates of premature ventricular complexes (incidence > 10/24 h: 100% vs. 20%; p = 0.048) and more severe spontaneous arrhythmia during stress test in mutant mice with MI as compared to control mice with MI. Mice with mitochondrial dysfunction exhibited longer spontaneous AV-blocks (467 ± 26 ms vs. 377 ± 24 ms; p = 0.013), an increased probability for induction of ventricular tachycardia during in vivo electrophysiological investigation (22% vs. 9%; p = 0.044), and a reduced conduction velocity in the infarct borderzone (38.5 ± 0.5 cm/s vs. 55.3 ± 0.9 cm/s; p = 0.001). Furthermore, mutant mice exhibited a significant reduction of the phospho-Cx43/Cx43 ratio in right (0.59 ± 0.04 vs. 0.85 ± 0.01; p = 0.027) and left ventricular myocardium (0.72 ± 0.01 vs. 0.86 ± 0.02; p = 0.023). Aging-related cardiac mosaic respiratory chain dysfunction facilitates the occurrence of spontaneous and inducible cardiac arrhythmia after myocardial infarction and is associated with slowing of electrical impulse propagation in the infarct borderzone. •Aging is physiologically associated with mitochondrial dysfunction.•Mitochondrial dysfunction leads to cardiac arrhythmia after myocardial infarction.•Slowing of electrical impulse propagation is found in the infarct borderzone.•Mitochondrial dysfunction is associated with alterations of phospho-Cx43.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.08.145