Altered cardiac mitochondrial dynamics with excessive fission is a predominant cause of cardiac dysfunction during ischemia/reperfusion (I/R) injury. Although pre-ischemic inhibition of mitochondrial fission has been shown to improve cardiac function in I/R injury, the effects of this inhibitor given at different time-points during cardiac I/R injury are unknown. Fifty male Wistar rats were subjected to sham and cardiac I/R injury. For cardiac I/R injury, rats were randomly divided into pre-ischemia, during-ischemia, and upon onset of reperfusion group. A mitochondrial fission inhibitor, Mdivi-1 (mitochondrial division inhibitor 1) (1.2 mg/kg) was used. During I/R protocols, the left ventricular (LV) function, arrhythmia score, and mortality rate were determined. Then, the heart was removed to determine infarct size, mitochondrial function, mitochondrial dynamics, and apoptosis. Our results showed that Mdivi-1 given prior to ischemia, exerted the highest level of cardioprotection quantitated through the attenuated incidence of arrhythmia, reduced infarct size, improved cardiac mitochondrial function and fragmentation, and decreased cardiac apoptosis, leading to preserved LV function during I/R injury. Mdivi-1 administered during ischemia and upon the onset of reperfusion also improved cardiac mitochondrial function and LV function, but at a lower efficacy than when it was given prior to ischemia. Taken together, mitochondrial fission inhibition after myocardial ischemic insults still exerts cardioprotection by attenuating mitochondrial dysfunction and dynamic imbalance, leading to decreased infarct size and ultimately improved LV function after acute cardiac I/R injury in rats. These findings indicate its potential clinical usefulness.
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August 2018
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A depiction of the mechanism of cellular autophagy showing the fusion of a lysosome with an autophagosome. The various molecules involved in the process can be seen alongside different microbes within the autophagosome. In this issue of Clinical Science, Li et al. (issue 15, pages 1645–1667) investigate the role of HMGB1-induced autophagy in liver fibrosis, and Andrade-Silva et al. (issue 16, pages 1725–1739) discuss the involvement of TLR2 and TLR4 in autophagy associated with cisplatin-induced acute kidney injury.
Research Article|
August 14 2018
Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury
Chayodom Maneechote;
Chayodom Maneechote
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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Siripong Palee;
Siripong Palee
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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Sasiwan Kerdphoo;
Sasiwan Kerdphoo
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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Thidarat Jaiwongkam;
Thidarat Jaiwongkam
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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Siriporn C. Chattipakorn;
Siriporn C. Chattipakorn
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
4Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand
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Nipon Chattipakorn
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
Correspondence: Nipon Chattipakorn (nchattip@gmail.com)
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Publisher: Portland Press Ltd
Received:
June 15 2018
Revision Received:
July 28 2018
Accepted:
July 31 2018
Accepted Manuscript online:
July 31 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (15): 1669–1683.
Article history
Received:
June 15 2018
Revision Received:
July 28 2018
Accepted:
July 31 2018
Accepted Manuscript online:
July 31 2018
Connected Content
A commentary has been published:
Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction
Citation
Chayodom Maneechote, Siripong Palee, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Siriporn C. Chattipakorn, Nipon Chattipakorn; Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury. Clin Sci (Lond) 16 August 2018; 132 (15): 1669–1683. doi: https://doi.org/10.1042/CS20180510
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